NIAID Funding News October 21, 2015

Feature Articles

Opportunities and Resources

In The News

Advice Corner

New Funding Opportunities

Header: Feature Articles.

Application Missteps—Unfocused Hypothesis or Specific Aims

After covering must-avoids like proposing a Weak Project and Misfiring on Innovation, we now tackle another pitfall to sidestep: lack of focus in your hypothesis and Specific Aims.

In this context, we use the term "unfocused" rather than "weak" since the two are different.

"Weak" relates to a project's impact and significance. Though an application may be weak, it can still be focused.

"Unfocused" relates to the lack of a strong central hypothesis, which can be too broad (e.g., inflammation is a key etiological component of autoimmune diseases) or too descriptive (e.g., we will evaluate changes in transcriptional signatures in the involved tissues following infection).

Why Focus Is Key

To paraphrase a popular saying, your application is only as strong as its weakest link—and you certainly don't want that link to be either your central hypothesis or your Specific Aims. One of our program officers explains why:

"An application with an unfocused central hypothesis or Specific Aims that won't rigorously test the underlying concepts will most likely not be discussed at review. These constitute the foundation of a project, so a lack of focus will strongly reduce reviewer enthusiasm for the project."—Alec Ritchie, Division of Microbiology and Infectious Diseases (DMID)

Hypothetically Speaking

Coming up with a solid central hypothesis for your application may be more challenging than you might think.

Not only should it be well-focused and testable (through your Specific Aims), but it has to be sound and important enough that reviewers believe your research will be able to make a high impact on its field.

With so much riding on your central hypothesis, it's crucial you think carefully about it, considering whether it forms a solid foundation for your Specific Aims.

To gauge the quality of your hypothesis, a program officer in our Division of AIDS (DAIDS) gives you a starting point:

"Ask yourself: Did I begin with a hypothesis then develop the aims and approach to address it? Or did I build the hypothesis around existing data and samples so it would fit what was available to me? The latter approach sometimes results in an unfocused hypothesis or the appearance of a 'data gathering' exercise."

What Makes a Good Hypothesis

From the perspective of reviewers as well as our program and scientific review staff, the saying "you'll know it when you see it" could apply to a focused (strong) hypothesis. In other words, there are not discrete definitions for focused and unfocused hypotheses. That said, our experts describe what does and does not make a good hypothesis.

DMID's Alec Ritchie offers this:

"Alone or together, these major factors contribute to an unfocused hypothesis: 1) insufficient or poorly interpreted preliminary data that the hypothesis is built upon and 2) unlikelihood of fully and objectively testing the hypothesis."

Another program officer, Wolfgang Leitner of our Division of Allergy, Immunology, and Transplantation (DAIT), echoes the sentiment about preliminary data as he describes two categories of suboptimal hypotheses:

"Those that are either based on weak preliminary data or not supported by the preliminary data (i.e., they may be very specific and focused but have no factual basis).

Then there are those that make the reader ask, ‘So what?' A hypothesis may not be considered strong because the research community doesn't think the question is interesting. It may have been answered already or it doesn't add anything to our understanding of the system. Therefore, confirming the hypothesis would have no significant impact on the field."

Jim Turpin, a program officer and branch chief in DAIDS, provides a lengthier description:

"A good central hypothesis is a balance of two components: an addressable scientific gap and the knowledge base needed to support the hypothesis. The knowledge base may come from supporting scientific literature or the investigator's experience and publication record.

Reviewers often judge the strength of a hypothesis by how these two factors synergize to create a compelling rationale for the proposed research. This synergy is often characterized as focus, which is important for how a reviewer perceives the hypothesis and its supporting Specific Aims."

For examples of effective and poorly focused hypotheses, go to Choose a Testable Hypothesis in our Strategy for NIH Funding, linked below.

Presenting Your Hypothesis

Once you've settled on a central hypothesis, you'll want to keep it fresh in reviewers' minds by mentioning it in various parts of your application. According to our experts, your hypothesis should feature prominently in at least two places: the abstract and Specific Aims.Wolfgang Leitner explains:

"The proposed project makes its first impression through the abstract and the Specific Aims sections, which consequently have a significant impact on how reviewers will score the entire application. Therefore, it is crucial for the central hypothesis, which the project is based on, to have a prominent position in these sections rather than to be introduced in the main body of the application."

Our DAIDS program officer suggests stating the hypothesis in the abstract and using a diagram in the Research Strategy to focus an application:

"Indicate what your hypothesis is early in the abstract so you don't lose reviewer interest. To help focus a pathogenesis or mechanistic application, consider including in the Research Strategy a diagram of the pathways hypothesized and tested. This diagram could help 1) the reader understand what is currently known and the gaps in knowledge that your project will address and 2) you better understand the analyses needed to test each hypothesis."

Frank DeSilva, a scientific review officer in our Scientific Review Program, addresses investigators responding to requests for applications (RFAs):

"It is important that the hypothesis is in line with the objective of the RFA and should be stated in the Specific Aims, which is one of the most important parts of an application since it serves as the first impression of an investigator's proposed research."

Getting Specific About Specific Aims

Your Specific Aims are the objectives for your research. To keep yourself from going off in too many directions, determine what two to four aims you could achieve within the proposed project period.

Focus your aims by making each one an achievable objective with clear endpoints your peer reviewers can easily assess.

Also maintain focus by never losing sight of your hypothesis, which goes hand in hand with the objectives of your project. In fact, the link between the hypothesis and aims is crucial, as two of our program officers point out:

"It's critical that the Specific Aims be designed to test the hypothesis as productively and directly as possible within the budget and timeline proposed, while allowing for pitfalls and alternative approaches to be negotiated as need be."—Alec Ritchie

"It must be clear to reviewers that the proposed aims are based on, and closely linked to, the central hypothesis. I would recommend paying close attention to the wording of the Specific Aims. Avoid (as much as possible) terms such as characterize, analyze, evaluate, or screen. They indicate a descriptive study that may not be asking mechanistic questions designed to address the central hypothesis."—Wolfgang Leitner

Focusing the Specific Aims Section

As part of your application's Research Plan, your Specific Aims section carries a lot of weight, despite its being limited to just one page (for R01s).

In it, you'll tell reviewers everything they need to know about the central hypothesis, research objectives, and significance of the proposed studies. Since all your reviewers read this part of your application, it's important to pack a punch by getting them excited about your project.

With little room to convey your aims, you'll want to keep them as focused as possible and cover the following bases:

  • Narrative that includes the "big picture" goal of your project and how the aims address an important scientific question or fill an important gap in understanding the big picture.
  • Statement of the central hypothesis and general approach you'll use to test it.
  • Brief description of your aims and how they build on your preliminary studies and previous research.

When responding to an RFA, the Specific Aims must address both what you propose to do and what the RFA is seeking, in terms of research objectives. Frank DeSilva provides some pointers for investigators applying to an RFA:

"The Specific Aims page should briefly describe the question(s) that you are trying to answer in response to the scientific objectives in the RFA, the stated hypothesis to address the question(s), a very brief background, and the significance of the work. Conclude with an impact statement stating how the results, if successful, will advance the scientific field of interest."

For advice on writing the Specific Aims section of your application, go to Explain Your Aims, and to see examples of focused Specific Aims, go to Sample Applications and Summary Statements. Both resources are linked below.

Related Links

Header: Opportunities and Resources.

Opportunity to Characterize Mycobacterial-Induced Immunity

Apply for exploratory/developmental research (R21) funds to perform hypothesis-generating research on the immunological responses that mediate protection from Mycobacterium tuberculosis (Mtb) infection or progression to active TB in HIV-infected or uninfected people.

The immune responses you study may be induced by mycobacterial infection, Bacillus Calmette-Guérin vaccine (BCG), or other investigational Mtb vaccinations. We're particularly interested in studies that include evaluating immune responses by anatomical location.

A secondary objective to this initiative is developing and testing new assays and technologies that allow for comparing mycobacterial-specific mucosal and systemic immunological pathways. Your new approaches could be used to monitor immune responses in preclinical studies and vaccine trials to advance Mtb vaccine development.

Your research approach should go beyond descriptive information already known about Mtb infection and responses to vaccines. The funding opportunity announcement (FOA) lists these approaches as interesting examples:

  • Elucidate mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms, throughout the course of mycobacterial infection or disease.
  • Analyze innate immune pathways and mechanisms in response to Mtb infection and/or TB progression, including the effect of mycobacterial infection on innate immune cell function and downstream activation of adaptive immune responses.
  • Effect of prior or chronic exposure to mycobacterial species or BCG vaccination or other candidate Mtb vaccines on subsequent immune responses to Mtb infection, TB reactivation, or disease reoccurrence.
  • Effect of Mtb or related mycobacteria infection of thymic epithelial cells on local or systemic host immune responses to Mtbinfection or candidate vaccines.
  • Identify and analyze immune response elicited during TB infection that may benefit mycobacterial persistence.
  • Develop novel functional assays to assess the host immune response against mycobacterial infections or candidate vaccines to increase information output or significantly minimize the amount of samples needed for a given evaluation.

This FOA will not support clinical trials nor projects that focus 1) solely on mechanisms of TB pathogenesis or 2) primarily on reagent or animal model development. (The latter may be included as necessary parts of the project if well-justified by the research aims.)

Applications are due on January 11, 2016, 2017, and 2018. AIDS applications have the same due dates.

For complete details, read the September 30, 2015 Guide announcement.

Header: Other News.

Summary of September Council: Budget, Concepts

The September 21, 2015 advisory Council meeting has come and gone, but you can still catch up on what transpired by reading this article and watching videocasts, linked below.

Director's Remarks

In his opening remarks, NIAID Director Dr. Anthony Fauci touched on various subjects, including the FY 2016 budget.

Budget, Continuing Resolution, Interim Paylines

The President's budget request for NIH included an increase of 3.3 percent or approximately $1 billion over the FY 2015 budget. For NIAID, a proposed increase of 4.5 percent from the FY 2015 budget level is composed entirely of earmarks allocated to HIV/AIDS research, universal flu vaccines, the NIH Precision Medicine Initiative, and combating antibiotic-resistant bacteria.

As Dr. Fauci predicted, NIH started the new fiscal year under a continuing resolution (CR), which continues government operations through December 11, 2015, at a flat budget relative to the FY 2015 enacted level. (Read NIAID Operates Under a Continuing Resolution, below.)

During the CR, NIAID has set interim R01 paylines at the 10 percentile for non-new PIs and the 14 percentile for new PIs. Stay tuned to our Paylines and Funding page for information as we receive it.

Departing Members

Dr. Fauci acknowledged the service of four members whose terms end on October 31:

  • Adaora Adimora, M.D., M.P.H
  • Mavis Agbandje-McKenna, Ph.D.
  • Jonathan Karn, Ph.D.
  • Georgia D. Tomaras, Ph.D.

As they leave Council, new members will take their place. We will introduce them in an upcoming issue.

Watch the entire Council presentation at NIAID Advisory Council Meeting—September 2015.

Other News

In other news, Dr. Fauci covered topics such as staff retirements and appointments, a tribute to former Congressman Louis Stokes, NIAID intramural scientists who garnered prestigious honors and awards, scientific conferences that NIAID participated in, and updates on Ebola.

Subcommittee Synopses

Learn more about NIAID's priorities and initiatives from Council subcommittee meetings, where NIAID staff discuss extramural research programs with advisory Council members.

See below for video of these subcommittees' open sessions:

Approved Concepts

The subcommittee meetings also covered concepts for clearance.

As you may know, Council must approve a concept before we can announce it as a possible initiative: request for applications, program announcement, or request for proposals.

To see a list of approved concepts, go to Concepts: Potential Opportunities. Find our most recent concepts on the following pages:

It's important to check out concepts since you can use them as clues to NIAID's research interests and potential topics for future investigator-initiated applications. Find out more at Unsolicited, Investigator-Initiated Research in our Strategy for NIH Funding.

Keep in mind that there's no guarantee that a concept will become a published initiative. For more on the planning process, go toConcepts May Turn Into Initiatives.

Learn More

To find out more about the activities of our advisory Council, go to:

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The Office of Extramural Research Welcomes a New Director

NIH has chosen Michael S. Lauer, M.D., to be the new deputy director for extramural research and director of the NIH Office of Extramural Research (OER).

Dr. Lauer received his M.D. from Albany Medical College in 1985, interned in medicine and served his residency at Massachusetts General Hospital and Harvard Medical School, and was a clinical fellow in medicine (cardiology) at Harvard Medical School and Beth Israel Hospital in Boston. He also served as a research fellow in the Framingham Heart Study at Boston University Medical School in Framingham, Massachusetts.

From 1993 to 2007, he held many leadership roles at the Cleveland Clinic, including professor of medicine, epidemiology, and biostatistics at the Clinic’s Lerner College of Medicine of Case Western Reserve University. He is a board-certified cardiologist, an elected member of the American Society of Clinical Investigation, and an elected fellow of the American College of Cardiology and the American Heart Association.

He began his distinguished service at NIH in 2007 as the director of the Division of Prevention and Population Science at the National Heart, Lung, and Blood Institute (NHLBI). Since 2009 he has served as the director of NHLBI's Division of Cardiovascular Sciences. In 2012, Dr. Lauer received the Arthur S. Flemming Award for exceptional service in federal government. He has been an active member of the Patient Centered Outcomes Research Institute (PCORI) since its inception in 2011 and has been a critical advisor for the President’s Precision Medicine Initiative.

His research interests have centered on clinical cardiovascular epidemiology, comparative effectiveness, and biostatistics. Dr. Lauer has also been actively involved and a strong advocate of human subjects protection. Besides these interests, he has longstanding interests in basic science and in medical editing—for seven years he was a contributing editor for the Journal of the American Medical Association.

Dr. Lauer takes over for Dr. Sally Rockey, who announced her resignation in A Farewell to NIH in June.

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News Briefs

NIAID Operates Under a Continuing Resolution. NIAID is operating under the Continuing Appropriations Act, 2016, which continues government operations through December 11, 2015, at 99.7892 percent of the FY 2015 enacted level. NIAID will issue noncompeting research grant awards at a level indicated on the most recent Notices of Award.

Find News and Resources From CSR. If you don't already subscribe to the Center for Scientific Review's Peer Review Notes, now's the time to check it out. Articles in the latest issue include Help Applicants at Your Institution by Using New CSR Outreach Resources and Understanding the Capacity of NIH’s Peer Review System.

Participate in National Biosafety Stewardship Month. October is National Biosafety Stewardship Month. NIH encourages grantee institutions to inspire a culture of safety and responsibility in research laboratories through enhanced training, engagement, and transparency. Learn more about health and safety requirements by reading the September 29, 2015 Guide notice.

Header: Advice Corner.

Understanding Indirect Costs

Having trouble distinguishing between direct and indirect costs for your federally funded research project? Check out the Office of Extramural Research’s (OER) YouTube presentation Indirect Costs 101. Pressed for time? Not to worry. We’ve listed a few key points below to help you better understand indirect costs.

NIH Has a Long History With Indirect Costs

NIH first began paying indirect cost rates during the 1950s, which were initially capped at 8 percent of the total award, then later increased to 20 percent. Additional guidance released in the 1958 Office of Management and Budget (OMB) Circular A-21 further defined indirect costs and explained what these costs could cover. In 1991, the indirect cost rate cap was again raised to 26 percent of the Modified Total Direct Cost (MTDC), but this cap applied to only administrative costs at universities and institutions of higher education.

Lastly, Uniform Guidance released in 2014 explained that federal agencies must accept and apply negotiated indirect cost rates to all federal awards, grants, and cooperative agreements. Exceptions are made to cap indirect costs only when the cap is required by a statute or is approved by the awarding federal agency head. This means that indirect cost rates are not typically required to adhere to a rate cap, depending on the program.

Knowing Which Costs to Consider Is Half the Battle

Totaling and attributing the sum of indirect costs can be as simple as a math equation, if you know what costs to consider.

Direct costs can be directly linked or assigned to a specific research project and consists of line items, such as personnel and travel.

Indirect costs (also referred to as “facilities and administrative” or “F&A”) are infrastructure costs that are not directly related to the project itself but are required to conduct the research and are critical to the success of the project and organization as a whole. Indirect costs would include line items such as payroll, departmental administration, building depreciation, student services, and the like.

Indirect Cost Rates Are Not Established by NIH, Except in Specific Cases

Indirect cost rates for colleges, universities, nonprofits, hospitals, and state and local governments are established in good faith by “cognizant agencies,” other than NIH. This determination, referred to as “cost negotiation cognizance,” is set by the HHS Division of Cost Allocation, or Department of Defense’s (DoD) Office of Naval Research. Your project’s indirect cost rate will be set by the agency you are receiving most of your funding from; i.e., HHS or DoD. However, once a federally-funded rate is negotiated and established, it applies to all government funding agencies that are going to support your grantee institution.

NIH sets indirect cost rates only when the grantee is a commercial organization. In these cases, the Division of Financial Advisory Services, Office of Acquisition Management and Policy will set the rate for the grantee organization.

In instances where the grantee institution does not have a negotiated rate at the time of its award and it does not wish to pursue negotiations to establish one, it can elect to receive a "de minimus" rate, which is 10 percent of MTDC. If the grantee institution does elect to utilize the de minimus rate, such rate must be used for all federal awards granted to that grantee institution, unless it should choose to negotiate for a rate, which it may apply to do at any time.

NIH also provides F&A costs without the need for a negotiated rate for certain classes of awards. See the following for additional information: What F&A costs will NIH provide for training, education, and career development grants? and What F&A costs will NIH provide for awards to foreign organizations, international organizations, and domestic grants with foreign components?

Total Cost Awards Have Drawbacks Too

Total Cost Awards (TCA) provide grantees with a previously determined funding level for an award, regardless of the indirect cost rate. Using a TCA, the funding federal agency can provide a total available award amount up front, but the grantee will need to work backwards and determine which portions of the award can be spent on indirect and direct costs.

TCA grants at NIH are rare. Though total cost awards tend to be easier for the funding agency to budget, we've seen investigators misjudge the amount of money available to complete their research. For this reason, NIH prefers to specifically list the amount of the award designated to direct and indirect costs.

Furthermore, in order to maximize fairness and competitiveness in peer review, NIH typically specifies the funds available for awards in direct costs. This way, peer reviewers judge applications' science in the context of comparable costs (i.e., direct costs).

One Hundred Percent of NIH Research Funding Supports Research

NIH research funding supports both direct and indirect costs associated with research. But non-research and research activities costs must be separated since NIH negotiates the indirect cost rate based on the F&A costs associated with research activities only. Instructional activities and other activities should be explicitly separated from research activities costs.

Additionally, facilities costs are also limited to the spaces that will be used only for research. Though separating activity costs may not seem beneficial, doing so ensures that the reimbursements issued on NIH grants solely support the conduct of research.

To learn more about indirect costs, see OER's Developing Your Budget, including What is the difference between allowable direct costs and allowable facilities & administrative (F&A) costs? For questions, contact NIH’s Division of Financial Advisory Services (DFAS).

More information is also available at Grants and Funding.

Header: Reader Questions.

Feel free to send us a question at 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.

“Can I request eligibility for the F31 Diversity grant? I am Filipino American, but Filipinos are not identified as a disadvantaged group in the NIH guidelines since they are categorized as Asians, even though Filipinos are greatly underrepresented in STEM fields.”—anonymous reader

No, you cannot request eligibility for the NRSA Individual Predoctoral Fellowship to Promote Diversity in Health-Related Researchaward, but you are eligible to apply for the NRSA Individual Predoctoral Fellowship award.

NIH’s current diversity policy is based on national race and ethnicity data. See Revisions to the Standards for the Classification of Federal Data on Race and Ethnicity from the Office of Management and Budget for official definitions.

Since the National Science Foundation does not report national subpopulation data, we cannot use it as a basis for eligibility. Also, note that NIH no longer uses institutional underrepresentation under Category A.

For more information, read Notice of NIH's Interest in Diversity and Research Training and Career Development FAQs—Diversity.

“Can I submit a new grant, modified from an unfunded resubmission (A1), using the exact same title?”—anonymous reader

Yes, you may use the same title again. Be sure to mark it as new in the application forms and eliminate any references to the previous review or previous review comments.

For more advice on sending an application as new, read our tutorial Option 2: Create a New Application in the Strategy for NIH Funding and refer to Frequently Asked Questions: Resubmissions of NIH Applications.

Header: New Funding Opportunities.

See other announcements at NIAID Funding Opportunities List.

Content last reviewed on October 21, 2015