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 ID: 708456
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Writing Specific Aims:The Cornerstone of a Successful Research Proposal
COL Kent KesterAssociate Dean for Clinical ResearchUSU School of Medicine
23 May 2013Slide2
What you should learn from this session
The importance and centrality of the Specific Aims section of a research proposalHow the Specific Aims section fits in to the larger research proposal and its developmentTo see some examples of successful Specific Aims submitted as part of research grant proposalsSlide3
Getting Research Grants Funded
Good ScienceHypothesisApproachGood MarketingWell-written proposal responsive to the program instructions
SALES!!!Slide4
Steps associated with the NIH grant application process
Berg, KM, et al. J Gen Int Med 2007;22:1587-95Slide5
Grant-writing timeline
Inouye, SK, et al. Ann Intern Med
2005;142:274-282Slide6
Grant-Execution Timeline
Inouye, SK, et al. Ann Intern Med 2005;142:274-282Slide7
Common Reasons for unfunded proposals
Lack of new ideasUnfocused research plan: poorly-written or unresponsive to program directionsLack on knowledge of published relevant workLack of essential scientific experienceFuture 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%Slide8
Define your goals
SpecificMeasurableRealisticSlide9
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.Slide10
Funding Sources
NIH/AHRQR01 Research Project GrantR03 Small Grant ProgramR15 Academic Research Enhancement AwardR21 Exploratory Research Grant
U01 Research Project Cooperative Agreement
K99/R00 Pathway to Independence Award
Other Federal Sources
DoD: MRMC, DHP, MILVAX, DTRA, DARPA
Infectious Disease, Combat
Casualty
Care, Military Operational Medicine, Regenerative Medicine, etc.
CDC
DVA
Others: USDA, USAID, FDA, etc.
Foundations/Nonprofits
Gates Foundation
Disease-specific foundations
Industry
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!Slide11
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 goalsStart with a concise problem statement and state why it is importantLimit 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 fieldSlide12
Know Your Audience
Align your project with defined research prioritiesParticularly relevant to DoD-funded medical research (e.g., what is really important to the DoD?)Identify who will be reviewing your proposalhttp://public.csr.nih.gov/StudySections/Pages/default.aspxKnow the evaluation criteria
NIH: significance, investigator, innovation, approach, environment
Others:
Find Out
if not specified (= do your homework!)Slide13
First Impressions of Your Proposal
TitleAbstract: the movie posterSpecific Aims: the movie trailerSlide14
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 jargonExplain specialized terminologyToo dense to read = too dense to fundKeep it general and interestingFocus on Why, Who, What, and HowSlide15
NIH Research Project Grant Review Criteria
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?Slide16Slide17Slide18
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?Slide19
The best research questions have significance and impact.
Does the project address an important problem (knowledge gap)?Novel antiviral drug: new mechanism of actionIdentification of previously-unrecognized pathway for viral or parasite development in insect vectors prior to transmission to humansIf the goals of the project are achieved
How will scientific knowledge or clinical practice be improved?
How will the field be changed?Slide20
Proposal should be based on a hypothesis
Hypothesis: a general statement, based on existing information, that describes a process in natureAllows one to make specific predictions that can be tested experimentallyProperties:Fit: compatible with existing knowledgeTestabilitySimplicity
Generality: applies broadlySlide21
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 fieldList the specific objectives of the research:
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 technologySlide22
A good format for a Specific Aims Section is a sandwich
First section: topic, goals, objectives, hypothesis, and rationaleSpecific Aims: objectives and descriptionHEADLINESLast paragraph: impact and outcomesConsider use of visual models in order to communicate a complex subject.Slide23
Writing Specific Aims
Create a bullet outlineConsider organizing bullets within four distinct paragraphs:Introductory paragraphWhat, Why, Who paragraphSpecific Aims paragraphPayoff 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.Slide24
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 applicationWhat 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 reviewerSlide25
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 mechanismsSlide26
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.Slide27
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 …Slide28
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.Slide29
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…Slide30
Describe the evidence for the hypothesis
For the first time, our published data from macaques support a direct enhancing effect of retrovirus pre-infection on malaria parasite growth, gametocytogenesis, and transmission.Prior studies conducted by our group have demonstrated novel interactions between unbound phenytoin and coronary endothelial cells.Slide31
Each specific aim has a short descriptive title and brief description
Aim 1: To determine the pathogenesis of the disease in vivoBased on our hypothesis, we predict that disruption of the interaction between XYZ and the ABC receptor will increase resistance to the diseaseAssess disease pathogenesis in mice with mutations in XYZ or the ABC receptorAssess disease resistance in mice treated with siRNA directed toward XYZ or the ABC receptorSlide32
Specific Aim Examples
Aim 1: Point prevalence of co-infectionWe 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 parasitemiaWe 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.Slide33
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 infectionThis 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.Slide34
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.Slide35Slide36
http://projectreporter.nih.gov/reporter.cfmSlide37
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.Slide38
And remember…
No amount of flowery language will overcome a skeptical audience.Propose good scienceWrite wellFollow the directionsGet feedbackSlide39
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):1587-1595.