Dr. Francis Collins, Director NIH
 About NIH and K awards
Contents of a K award
  Research Strategy
Institutes or Centers (ICs) each has its own

 Mission
 Budget
 Activities
 Ways of doing things
 Own personality

When you’re planning to submit a grant, check with program
directors from different institutes to determine their specific
policies and interest in your science.
New Investigator
 Has not been PI on a significant NIH research grant (R01)
Can have held small research grants (e.g., R03, R21), K
awards, Fellowships (F)

Early Stage Investigator (ESI)
A new investigator within 10 years of doctorate or
completing residency

Status defined in your eRA Commons profile
 US Citizens, Non-Citizen Nationals, Permanent Residents (except

 Must devote a minimum of 75% effort to research and career
 development activities

 Previous NIH Principal Investigators may be Ineligible
 Principal Investigators on R03 or R21 are eligible to apply (except

 Principal Investigators on R01 or subproject Principal Investigators
 on a P01 are not eligible to apply.
Program Description
K01       Mentored Research Scientist Development Award
          Career development in a new area of research

K08       Mentored Clinical Scientist Research Development Award
          Career development for those with clinical doctoral degree in biomedical/behavioral research,
          including translational research—if patient research, see K23.
K07       Academic Career Award
          Developmental of junior candidates; leadership for individuals in improving curricula and enhancing
          research capacity.
K23       Mentored Patient-Oriented Research Career Development Award
          Development of the independent research scientist for patient research—if not patient-oriented
          research in biomedical area, see K08.
K25       Mentored Quantitative Research Career Development Award
          To foster interdisciplinary collaboration in biomedical research by supporting career development
          experiences for scientists with quantitative and engineering backgrounds.

K99/R00   NIH Pathway to Independence Award. Provides 5 years’ support in 2 phases:
          I.1-2 years of mentored support for highly promising postdoctoral fellows.

          I.Up to 3 years of independent support contingent on securing an independent research position.
Program   Description
K22       Career Transition Award
          Support to an individual postdoctoral fellow in transition to a faculty

K99/R00   NIH Pathway to Independence Award. Provides 5 years’ support in 2

          I.1-2 years of mentored support for highly promising postdoctoral
          II.Up to 3 years of independent support contingent on securing an
          independent research position.
Program   Description
          Independent Scientist Award
          Develop the career of the funded scientist.
          Senior Scientist Award
K05       For outstanding scientists with a sustained level of high productivity.
          Funding determined by the sponsoring Institute.

          Midcareer Investigator Award In Patient-Oriented Research
K24       Development of clinical mentors conducting funded research.

          Mentored Quantitative Research Career Development Award
          To foster interdisciplinary collaboration in biomedical research by
K25       supporting career development experiences for scientists with quantitative
          and engineering backgrounds.
                                                 U-Series Cooperative Grants

   NRSA            NRSA                              SBIR, STTR R41/R42
  Predoc          Postdoc
                                               P-Series Program Project/Center
  F30, F31          F32                           Small Research Grant R03

   Predoc         Postdoc                  Exploratory/Development Grant R21
    T32             T32
                                                 Research Project Grant R01

 Grad or         Postdoc or      Early                Middle              Senior
Med School       Residency

                Pathway to       Ment Research           Midcareer             Senior
              Independence            K01                 Patient-            Scientist
                                 Ment Clinical           Oriented            Award K05
                                     K08                    K24
             Career Transition                                                NRSA Senior
                Award K22        Ment Patient-          Independent          Fellow F33
                                  Orient K23            Scientist K02

                                  Ment Quant
                                   RCDA K25
                                 K Contents
Section                           Material Requested

                                  Candidate background
Candidate Information & Career
                                  Career Goals and Objectives
Development Plan
                                  Career Development & Training Activities             12 pg
Research Plan                     Specific Aims + Research Strategy

Statements of Support             Statements by Mentor, Co-Mentor, Consultants

                                  Description of Institutional Environment
Environment and Institutional
Commitment to Candidate           Institutional Commitment to Candidates Research Career

                                  3-5 reference letters not from the Mentor/Co-Mentor

                                  From established scientists (referees) that address candidate’s
                                  qualifications, training, interests and potential for becoming an
Letters of Reference              independent scientist

   Candidate background

   Career Goals and Objectives

   Career Development/Training Activities

   Training in Responsible Conduct of Research
   Detail your professional responsibilities at Dartmouth and
    elsewhere and their relation to proposed K activities

   Your prior training and how it relates to your objectives and
    long-term career plans

   Your previous research efforts, including any publications, prior
    research interests, and experience (not detailed in biosketch)

   Trajectory to an independent investigator
   How does the award fit into past and future research
    career development?

   If there are consistent themes or issues that have guided
    previous work, make them clear
       If your work has changed direction, give the reasons

   It is important to justify the award and how it will enable
    you to develop or expand your research career
       Include a timeline and plan to apply for subsequent grant support
   Describe new/enhanced research skills and knowledge you
    will acquire

   For mentored awards, describe structured activities—
    coursework or technique workshops—which are part of the
    developmental plan

   Discuss each activity, include a percentage of time by
    year, explain how activity relates to the proposed
    research and the career development plan
 You MUST include a plan for instruction in responsible
  conduct of research (RCR). Now 1 page outside of the 25.
 If you fail to include one or it’s inadequate, your
  application will be incomplete and won't be reviewed
  until you provide an acceptable plan of instruction.
 You must include 5 instructional components:
   1.   Format of instruction
   2.   Subject matter
   3.   Faculty participation
   4.   Duration
   5.   Frequency

   Mentor, co-mentor, collaborators’, consultants’
    and contributors’ statements—6 pages total

   Reference letters— 3-5 total
       Critically important and should address the candidate's
        competence and potential to develop into an
        independent investigator
       Cannot be your mentor/co-mentor
       Uploaded to ERAcommons
 A great program and stellar academic record
  help, but to get the best score, you need to
  show reviewers that you can establish a
  research career
 Your career development plan is as important
  as your Research Plan
   Explain how K will be a vital step toward your ultimate career
    goal and move you toward scientific independence
   Outline both career development plan and research plan to
    see common elements
   Specify training and courses that you will participate in, how
    often you'll meet with consultants, and how all of this will
    help you reach independence

        Current Research Plan                Restructured Research Plan
1. Introduction to Application           1. Introduction to Application

2. Specific Aims                         2. Specific Aims
3. Background and Significance           3. Research Strategy
                                         a. Significance
4. Preliminary Studies/Progress Report   b. Innovation
5. Research Design and Methods           c. Approach (incl. Preliminary Studies)

6-12                                     4-10 (renumbered)
13. Select Agent Research                11. Select Agent Research (Modified)
14-17                                    12-15 (renumbered)
①   State concisely the goals of the proposed research and summarize the
    expected outcome(s), including the impact that the results of the
    proposed research will exert on the research field(s) involved.

②   List succinctly the specific objectives of the research proposed, e.g.

o   test a stated hypothesis
o   create a novel design
o   solve a specific problem
o   challenge an existing paradigm or clinical practice
o   address a critical barrier to progress in the field, or
o   develop new technology
   FIRST paragraph– Define the problem/critical need and gap(s) in
    knowledge—short background leading up to the stated problem and
    knowledge gap

   Proposed solution to problem and gap by proposing hypothesis(es)

   Specific Aims –Objectives that test the hypotheses addressing the
    critical need
        e.g., to develop, determine, identify…
        Avoid vague aims, e.g., “to explore”

   Expected Outcomes leading to impact on the field

   Impact – probability your study will be successful and will exert a
    powerful sustained influence on the field (derived from
    significance and innovation)
        If it won’t work, it has no impact, even with high significance
        Address the immediate problem AND your long-term goals
   The Problem Colon cancer is a fatal disease if not
    detected early. Current medical practice in the US is
    screening colonoscopies for all over age 50, but
    colonoscopies are expensive and invasive. Screening for
    occult blood in stool is inexpensive but ineffective, and
    many cancers are missed. A blood test that could
    accurately detect colon cancer very early would save
   Gaps in Knowledge Current approaches for measuring
    proteins in blood are relatively insensitive, and unlikely to
    detect cancers early enough. Human variability and low
    signal means many independent patient samples must be
   The Solution New proteomic technologies developed by
    my group offer both the sensitivity and throughput needed
    to identify and validate blood biomarkers for early
    detection of colon cancer.
   Hypothesis We hypothesize that colon cancers can be
    more effectively detected using sensitive blood
   Action Plan
Specific Aim 1: To identify plasma proteins associated with early stages of colon
   cancer using novel mass spectrometric approaches that provide absolute
   protein abundance measurements down to pg/ml levels. These measurements
   will be applied to a unique cohort of colon cancer patients available from
   clinical collaborators
Specific Aim 2: To carry out a bioinformatic analysis of over-represented
   proteins for enrichment of specific functions using a variety of software tools
   including KEGG, BIND, and MetaCor
Specific Aim 3: To select and validate candidate biomarkers
Candidate biomarkers selected on the basis of functions known to be associated
   with carcinogenesis will be verified by orthogonal approaches. The top ten
   ten verified candidates will be assessed in 1000 prospectively collected
   plasma samples from early stage colon cancer patients, using a novel high
   throughput proteomics approach
   Expected Outcomes and Impact
The end product of this research will be an affordable
  accurate blood test for early detection of colon cancer
  without colonoscopy. Our approach will use many
  previously successful methods (preliminary studies) to
  increase the probably of success in this proposal.
Successful demonstration of this approach in colon cancer
  will enable application to other cancers in need of early
  detection biomarkers. Future directions of this research
  also include the application of a systems biology
  approach to the large datasets generated in the
  discovery phase that will provide new insights about the
  earliest stages of colon cancer.
①   Explain the importance of the problem or critical barrier
    to progress in the field that the proposed project

②   Explain how the proposed project will improve scientific
    knowledge, technical capability, and/or clinical practice
    in one or more broad fields.

①   Describe how the concepts, methods, technologies,
    treatments, services, or preventative interventions that
    drive this field will be changed if the proposed aims are
①   Explain how the application challenges and seeks to shift
    current research or clinical practice paradigms.

②   Describe novel theoretical concepts, approaches or
    methodologies, instrumentation or intervention(s) to be
    developed or used, and any advantage over existing
    methodologies, instrumentation or intervention(s).

③   Explain refinements, improvements, or new applications
    of theoretical concepts, approaches or methodologies,
    instrumentation or interventions.
①   Describe the overall strategy, methodology, and analyses
    to be used to accomplish the specific aims of the project.

②   How will data be collected, analyzed, and interpreted as
    well as any resource sharing plans as appropriate?

③   Discuss potential problems, alternative strategies, and
    benchmarks for success anticipated to achieve the aims.

④   If the project is in the early stages of development,
    describe any strategy to establish feasibility, and address
    the management of any high-risk aspects of the proposed
   Preliminary Studies/Progress Report

   Study design/study strategy

   Experimental approach
        Experiments to address each SA
        Emphasize
            Unique methods but abbreviate standard methods, especially if
             used in “Preliminary Studies”
            Methods not previously used — collaborators
        Use tables and figures to illustrate complex experiments with multiple
         arms or repetitions under different conditions—Study Design

   Interpretation of results
        Even if your experiment is well designed, its interpretation is vital to
         the reviewer
        Link the interpretation to your proposed SA and hypothesis
   Potential Pitfalls and Alternative Approach
       Roadblocks to your experimental approach and how you would adjust
        the approach to move forward
       Failure to see weak points gives reviewers impression your approach is
        careless and less likely to succeed

   For early-stage PI, strategy to establish feasibility with
   Future Directions
       Discuss what’s likely not feasible for this grant period, and what your
        future studies will focus on
       Focus on gaining independence with plans for an R01

   Milestones and Timeline
       By each aim, provide quantitative benchmarks for assessing your
        progress over the grant years
  Candidate               Research Strategy   Career Development Plan

Environment/Institution                       Mentor/Consultants
Describe the qualities and potential of the candidate with
  reference to:
①   Potential for conducting research

②   Evidence of originality

③   Adequacy of scientific background

④   Quality of research endeavors/publications to date

⑤   Commitment to health-oriented research

⑥   Need for further research experience and training
   Strong publication history: 2 or more first author, handful
    of middle author

   Quality of the application itself
       Writing of high quality and easy to follow
       Attention to detail for administrative items like vert. animals
       Completeness, clearly shows significant time invested

   Clarity of intention to be a leader in academic biomedical
    research reflected in letters and mentor statement
       Letters with enthusiastic support
         Career Development Plan—VERY IMPORTANT

   This is training: how will it extend your abilities?
   Include some short or long courses to strengthen new
   List journal clubs, lab meetings, seminars, national
   Show how you will improve on your weaknesses and make
    an academic niche you can thrive in

   Primary mentor must write an impressive Mentor
       Discuss candidate potential for independence
       Discuss training skills, commitment, and history

   Secondary mentors should support your weak areas and
    support training in those areas

   Primary mentor should make clear that your research is
    your own and they will not compete with you
                      Research Strategy
   Easy to follow
   Doable
   Not overly ambitious
   Obvious impact
   How will it put you in a position to be independent at the
   Will it lead to a long-term research program?
      How will the K work lead to an R grant?
 About HF Awards
Contents of a Hitchcock award
   Candidate
   Research Strategy
   To increase the pool of extramurally funded, clinically
    oriented researchers at Dartmouth-Hitchcock Medical
    Center and Dartmouth College.

   Three-year career development awards to promising
    young investigators committed to clinically oriented
    research and who are members of academic
    departments equally committed to their careers.
   Applicants must hold a terminal degree appropriate to
    their discipline, though they may not have progressed
    beyond the rank of Assistant Professor, and may not
    currently have significant levels of extramural support.

    Clinicians must have completed their clinical training
    at the initiation of the award.

   Must devote a majority of their effort to research and
    research training during the course of the award.
   Total of $300,000 over 3 years toward salary

   Additional $25,000/y for research and career

   Funding for year 2 and 3 contingent on progress
       60-90 days before 1st and 2nd Award years, you will submit a
        report detailing progress toward the goals
       Recipient and mentor present and discuss research and
        progress with HF Scholar review committee

   Department must commit matching research salary
    support equivalent to half of that provided by The
    Hitchcock Foundation.
Career Development Plan

   Training—1 page
       Plan for training necessary to launch an independent career
       Courses in biostatistics, epidemiology, RCR, etc
       Proposed subjects, format, frequency, duration

   Mentor’s Plan/Expectations— 1 page
       Statement from mentor on your qualifications
       Type and extent of supervision

   Institutional Commitment— 1 page
       Research space (office and/or lab), resources, and support
        personnel available
       Clinicians: proposed clinical schedule
Research Plan

   Long-term Goals—1 page
       What specific area are you studying?
       Why is it important?
       What kinds of questions will you answer?

   Research Proposal—3-4 pages + references
       Specific Aims with hypotheses
       How will they be tested/measured?
       Anticipated results
       Pitfalls and alternative methods
       Follow the format of the Hitchcock Foundation Pilot Grants
        protocol (handout)
   Potential to develop into an independent researcher
       Candidate’s prior academic record
       productivity and commitment to research
   Institutional commitment
       Mentor’s participation in crafting a strategic career
        development plan
       Departmental salary support and plan to minimize the clinical
        and administrative burdens of the applicant
   Research training
       Appropriateness of the proposed educational activities, and the
        consistency of the career development plan with the
        candidate's career goals
   Research design
       Importance of the question being asked and the clarity and
        validity of the method proposed to address it

   Research significance
       Importance of the research

   Research fit
       How the proposed course of research and research training
        draws on available expertise at Dartmouth

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