Writing Specific Aims:
The Cornerstone of a Successful
Research Proposal
COL Kent Kester
Associate Dean for Clinical Research
USU School of Medicine
23 May 2013
What you should learn from this session
• The importance and centrality of the Specific
Aims section of a research proposal
• How the Specific Aims section fits in to the
larger research proposal and its development
• To see some examples of successful Specific
Aims submitted as part of research grant
proposals
Getting Research Grants Funded
• Good Science
– Hypothesis
– Approach
• Good Marketing
– Well-written proposal responsive to the program
instructions
SALES!!!
Steps associated with the NIH grant
application process
Berg, KM, et al. J Gen Int Med 2007;22:1587-95
Grant-writing timeline
Inouye, SK, et al. Ann Intern Med 2005;142:274-282
Grant-Execution Timeline
Inouye, SK, et al. Ann Intern Med 2005;142:274-282
Common Reasons for unfunded
proposals
• Lack of new ideas
• Unfocused research plan: poorly-written or unresponsive
to program directions
• Lack on knowledge of published relevant work
• Lack of essential scientific experience
• Future directions of research?
• Questionable experimental approach
• Unrealistic scope of work
• Lack of experimental detail
• Limited funding: major issue at present
– FY13: NIAID R01 new investigator 12%; established investigator
8%
Define your goals
• Specific
• Measurable
• Realistic
Specific Aims:
The Cornerstone of the entire research proposal
• What do you want to accomplish (objectives)?
– This is the master plan for your research.
– Not unusual for some members of the study section to read only the Specific
Aims and Project Summary/Abstract before scoring.
• Dense, full-of-jargon, poorly-written Specific Aims will not help the scoring of your
proposal, even if the science is sound!
– Is a useful summary for obtaining early feedback on your proposal
• Includes project milestones, hypotheses to be tested—all the key aspects
of your project (e.g., what is important and exciting) without fine detail
• Aim for an unmet scientific need
• Be crystal-clear in your writing!
– You provide the conceptual framework upon which the reviewers hang the
details of what will be done.
Funding Sources
NIH/AHRQ
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R01 Research Project Grant
R03 Small Grant Program
R15 Academic Research
Enhancement Award
R21 Exploratory Research Grant
U01 Research Project Cooperative
Agreement
K99/R00 Pathway to Independence
Award
Other Federal Sources
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DoD: MRMC, DHP, MILVAX, DTRA,
DARPA
– Infectious Disease, Combat Casualty
Care, Military Operational Medicine,
Regenerative Medicine, etc.
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CDC
DVA
Others: USDA, USAID, FDA, etc.
Foundations/Nonprofits
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Gates Foundation
Disease-specific foundations
Industry
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Research or clinical trials support
CRADAs, grants, or in-kind funding
In many cases, the standard NIH format for organization of your grant
proposal is often preferred. Read the submission instructions!
Specific Aims: Often the Hardest Part of the
Proposal to Write
• The most important part of your proposal—you have
to “SELL” your research idea!
– Understand your customer (e.g., Study Section reviewers)
– Show that you will help NIH (or DoD, DVA, etc.) accomplish
its goals
• Start with a concise problem statement and state why
it is important
• Limit yourself to 2-4 aims
• Be declarative
• Make sure to explain why the research matters
• Final product: A well-crafted project that will result in
the advancement of significant knowledge in your field
Know Your Audience
• Align your project with defined research priorities
– Particularly relevant to DoD-funded medical research
(e.g., what is really important to the DoD?)
• Identify who will be reviewing your proposal
– http://public.csr.nih.gov/StudySections/Pages/default.
aspx
• Know the evaluation criteria
– NIH: significance, investigator, innovation, approach,
environment
– Others: Find Out if not specified (= do your
homework!)
First Impressions of Your Proposal
• Title
• Abstract: the movie poster
• Specific Aims: the movie trailer
Themes for Specific Aims
• Convince the reviewers that the funding will be a
good return on investment (SALES)
• Write for a general science audience; don’t bury your
aims in too much jargon
• Explain specialized terminology
– Too dense to read = too dense to fund
• Keep it general and interesting
– Focus on Why, Who, What, and How
NIH Research Project Grant Review Criteria
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Significance: is the work important?
Innovation: is it new thinking?
Approach: is it feasible?
Investigator(s): are they well-suited?
Environment: is there adequate support and
resources?
It is essential to start with a good question.
• What is the mechanism of X?
• Is this drug/vaccine/diagnostic device better
than the current standard?
• Does this new curriculum result in enhanced
learning?
• Does this change in clinical practice improve
clinical outcomes?
The best research questions have significance
and impact.
• Does the project address an important problem
(knowledge gap)?
– Novel antiviral drug: new mechanism of action
– Identification of previously-unrecognized pathway for viral
or parasite development in insect vectors prior to
transmission to humans
• If the goals of the project are achieved
– How will scientific knowledge or clinical practice be
improved?
– How will the field be changed?
Proposal should be based on a hypothesis
Hypothesis: a general statement, based on existing
information, that describes a process in nature
– Allows one to make specific predictions that can be
tested experimentally
Properties:
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Fit: compatible with existing knowledge
Testability
Simplicity
Generality: applies broadly
Elements of a Specific Aims Page
• Concise statement of the goals of the proposed
research and a summary of the expected
outcomes, including impact on the field
• List the specific objectives of the research:
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Test a hypothesis
Create a novel design
Solve a specific problem
Challenge an existing paradigm or clinical practice
Address a critical barrier to progress in the field
Develop new technology
A good format for a Specific Aims Section is a
sandwich
• First section: topic, goals, objectives, hypothesis,
and rationale
• Specific Aims: objectives and description
– HEADLINES
• Last paragraph: impact and outcomes
• Consider use of visual models in order to
communicate a complex subject.
Writing Specific Aims
• Create a bullet outline
• Consider organizing bullets within four distinct
paragraphs:
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Introductory paragraph
What, Why, Who paragraph
Specific Aims paragraph
Payoff paragraph: helps to develop advocacy for your
proposal among the majority of reviewers who will
not, in all likelihood, have read the complete
application
• There should be at least one important expected outcome
for each of your aims.
First paragraph: provides the rationale for the
proposed study(ies)
• What is the Topic?
– Opening sentence needs to be interest-grabbing.
• Statement of current knowledge: will help less-expert panel members get
up to speed with respect to what is know about the topic of the
application
• What is the Gap in knowledge?
– The gap in knowledge is what is holding back the field and is what you
will address in the application.
• What is the long-term Goal of your research?
• What are the specific Objectives for the proposal?
• What is the Hypothesis?
• What is the evidence for the hypothesis?
• What is the Rationale/Significance?
GOAL: half-page or less (~300 words) to set the stage and to interest the
reviewer
Start the Specific Aims with a concise, active
statement introducing the topic of the proposal
• In sub-Saharan Africa, co-infection with HIV worsens
clinical malaria and has resulted in an additional 3
million cases of clinical malaria and 65,000 deaths.
• Diabetes is a major health concern in the U.S.
• Molecular analysis has emerged as one of the most
powerful tools to determine antimicrobial resistance
mechanisms
Describe the gap in knowledge or unmet need
that the proposal will address
• There is a critical gap in our knowledge about the
impact of HIV on asymptomatic malaria and how HIV
may impact the ability of adults to serve as efficient
reservoirs of disease.
• But the incidence of diabetes continues to rise.
• Management of parasitic diseases depends largely
on chemotherapy but anti-parasitic drug treatments
has multiple challenges.
Describe your goals
• Our long-term goal is to understand how
behavioral modification can prevent the early
onset of diabetes.
• The goal of our research is to determine the
mechanism of X (or Y, or Z).
• The overall goal of our research group is to
define the role of …
Describe the specific objectives
• We propose to focus a series of complementary
clinical and entomological studies using highly
sensitive and specific molecular tools in a highly
endemic area of western Kenya to address…
• This proposal will focus on testing behavioral
interventions in the institutionalized elderly.
• We propose to develop artificial intelligence
algorithms for the analysis of thought-related
changes in cerebral perfusion.
Define the underlying hypothesis
• We hypothesize that HIV itself, and the treatment used
routinely for opportunistic infection prophylaxis, contribute to
excess malaria burden by increasing the prevalence of
asymptomatic adult reservoirs that experience frequent and
prolonged periods of transmissible sub-microscopic
gametocytema.
• Both of these responses are unique to a subset of enterococci
exhibiting the Van-A phenotype, and we hypothesize that
they are essential for the pathogenesis of…
Describe the evidence for the hypothesis
• For the first time, our published data from macaques
support a direct enhancing effect of retrovirus preinfection on malaria parasite growth,
gametocytogenesis, and transmission.
• Prior studies conducted by our group have
demonstrated novel interactions between unbound
phenytoin and coronary endothelial cells.
Each specific aim has a short descriptive title
and brief description
• Aim 1: To determine the pathogenesis of the
disease in vivo
– Based on our hypothesis, we predict that
disruption of the interaction between XYZ and the
ABC receptor will increase resistance to the
disease
a. Assess disease pathogenesis in mice with mutations
in XYZ or the ABC receptor
b. Assess disease resistance in mice treated with siRNA
directed toward XYZ or the ABC receptor
Specific Aim Examples
• Aim 1: Point prevalence of co-infection
– We will determine whether the prevalence and magnitude of
peripheral parasitemia, and specifically gametocytemia, are greater in
untreated HIV-positive adults than in HIV-negative adults. These data
will reveal whether untreated HIV-infected persons are, in fact, more
efficient reservoirs of malaria.
• Aim 2: Longitudinal prevalence of asymptomatic
parasitemia
– We will compare the incidence, intensity, and duration of
asymptomatic malaria parasitemia in general, and gametocytemia
specifically, in HIV-negative adults, in HIV-positive adults on TS only,
and in HIV-positive adults on TS plus ART. We will measure the impact
of prolonged TS therapy on gametocyte carriage.
The last paragraph focuses on innovation,
impact, and outcomes
• Innovation:
– To our knowledge, this proposal is the first attempt to use
microarray technology to discern differential patterns in human
gene activation associated with experimental malaria infection
– This proposal applies two state-of-the-art techniques to
understand the pathogenesis of sarcoidosis.
– Note that innovation doesn’t always mean the use of the latest
molecular biology tools and techniques.
• Outcomes and Impact:
– The experiments described in this proposal will provide a
complete description of the mechanism…
– Understanding the pathogenesis of this disease will lead to new
therapeutic approaches.
Additional Details
• Make sure that research proposal is properly
aligned with the funding program (= read the
directions)
• Get feedback!
• Make sure that there are no stray regulatory
compliance issues (like human subjects or
animal welfare). Ignoring these aspects can
doom your proposal.
http://projectreporter.nih.gov/reporter.cfm
Some final thoughts
• Lay out your aims so clearly so that the reviewers
understand them without having to read things more
than once.
• Lead the reviewer down a logical trail of ideas that
makes the conclusion of what is being proposed to
be done is inescapable. One can include a relevant
quotation from the NIH Director or an excerpt from
an NIH strategic research plan).
• Pique the reviewer’s interest—help them share your
sense that there is an important mystery to be
solved.
And remember…
• No amount of flowery language will overcome
a skeptical audience.
– Propose good science
– Write well
– Follow the directions
– Get feedback
References
Inouye SK, Fiellin DA. An evidence-based guide
to writing grant proposals for clinical research.
Annals of Internal Medicine 2005;142:274-282.
Berg KM, Gill TM, Brown AF, et al. Demystifying
the NIH grant application process. Journal of
General Internal Medicine 2007;22(11):15871595.