Dr. Francis Collins, Director NIH
 About NIH and K awards
Contents of a K award
Candidate
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
K99/R00)
 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
K99/R00)
 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
position.
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.
II.Up to 3 years of independent support contingent on securing an
independent research position.
Program
Description
K02
Independent Scientist Award
Develop the career of the funded scientist.
K05
Senior Scientist Award
For outstanding scientists with a sustained level of high productivity.
Funding determined by the sponsoring Institute.
K24
K25
Midcareer Investigator Award In Patient-Oriented Research
Development of clinical mentors conducting funded research.
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.
U-Series Cooperative Grants
SBIR, STTR R41/R42
NRSA
Predoc
NRSA
Postdoc
F30, F31
F32
Small Research Grant R03
Postdoc
T32
Exploratory/Development Grant R21
Predoc
T32
Grad or
Med School
Postdoc or
Residency
Pathway to
Independence
(K99/R00)
Career Transition
Award K22
P-Series Program Project/Center
Research Project Grant R01
Early
Ment Research
K01
Middle
Ment Clinical
K08
Midcareer
PatientOriented
K24
Ment PatientOrient K23
Independent
Scientist K02
Ment Quant
RCDA K25
Senior
Senior
Scientist
Award K05
NRSA Senior
Fellow F33
K Contents
Section
Material Requested
Candidate Information & Career
Development Plan
Candidate background
Career Goals and Objectives
Career Development & Training Activities
Research Plan
Specific Aims + Research Strategy
Statements of Support
Statements by Mentor, Co-Mentor, Consultants
12 pg
Description of Institutional Environment
Environment and Institutional
Commitment to Candidate
Institutional Commitment to Candidates Research Career
Development
3-5 reference letters not from the Mentor/Co-Mentor
Letters of Reference
From established scientists (referees) that address candidate’s
qualifications, training, interests and potential for becoming an
independent scientist
13

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
18

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
20
Current Research Plan
Restructured Research Plan
1. Introduction to Application
1. Introduction to Application
2. Specific Aims
2. Specific Aims
3. Background and Significance
5. Research Design and Methods
3. Research Strategy
a. Significance
b. Innovation
c. Approach (incl. Preliminary Studies)
6-12
4-10 (renumbered)
13. Select Agent Research
11. Select Agent Research (Modified)
14-17
12-15 (renumbered)
4. Preliminary Studies/Progress Report
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
o
o
o
o
o
test a stated 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, or
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
lives.

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
measured.

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
biomarkers.

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
addresses.
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
achieved.
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
work.

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
methods

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
35
Candidate
Environment/Institution
Research Strategy
Career Development Plan
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

Candidate
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
areas

List journal clubs, lab meetings, seminars, national
meetings

Show how you will improve on your weaknesses and make
an academic niche you can thrive in
Mentor

Primary mentor must write an impressive Mentor
Statement


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
end?
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
development

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




Mentor’s Plan/Expectations— 1 page



Plan for training necessary to launch an independent career
Courses in biostatistics, epidemiology, RCR, etc
Proposed subjects, format, frequency, duration
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



Institutional commitment



Candidate’s prior academic record
productivity and commitment to research
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


Research significance


Importance of the question being asked and the clarity and
validity of the method proposed to address it
Importance of the research
Research fit

How the proposed course of research and research training
draws on available expertise at Dartmouth