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)
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.