Dr. Francis Collins, Director NIH

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About NIH and K awards

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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 K08 K07 K23 K25 Mentored Research Scientist Development Award

Career development in a new area of research

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.

Academic Career Award

Developmental of junior candidates; leadership for individuals in improving curricula and enhancing research capacity.

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.

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 K22 K99/R00 Description Career Transition Award

Support to an individual postdoctoral fellow in transition to a faculty position.

NIH Pathway to Independence Award.

Provides 5 years ’ phases: support in 2 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 K02 K05 K24 Description Independent Scientist Award

Develop the career of the funded scientist.

Senior Scientist Award

For outstanding scientists with a sustained level of high productivity. Funding determined by the sponsoring Institute.

Midcareer Investigator Award In Patient-Oriented Research

Development of clinical mentors conducting funded research.

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.

NRSA Predoc F30, F31 Predoc T32 NRSA Postdoc F32 Postdoc T32 U-Series Cooperative Grants SBIR, STTR R41/R42 P-Series Program Project/Center Small Research Grant R03 Exploratory/Development Grant R21 Research Project Grant R01 Grad or Med School Postdoc or Residency Pathway to Independence (K99/R00)

Career Transition

Award K22 Early Middle Senior Ment Research K01 Ment Clinical K08 Ment Patient Orient K23 Ment Quant RCDA K25 Midcareer Patient Oriented K24 Independent Scientist K02 Senior Scientist Award K05 NRSA Senior Fellow F33

Section Candidate Information & Career Development Plan Research Plan Statements of Support Environment and Institutional Commitment to Candidate

K Contents

Material Requested

Candidate background Career Goals and Objectives Career Development & Training Activities Specific Aims + Research Strategy Statements by Mentor, Co-Mentor, Consultants

12 pg

Description of Institutional Environment Institutional Commitment to Candidates Research Career Development 3-5 reference letters not from the Mentor/Co-Mentor From established scientists (referees) that address candidate independent scientist ’ s qualifications, training, interests and potential for becoming an

Letters of Reference

13

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Candidate background

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Career Goals and Objectives

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Career Development/Training Activities

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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.

4.

5.

Faculty participation Duration Frequency 18

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Mentor, co-mentor, collaborators

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, consultants

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and contributors

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statements—6 pages total

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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

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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

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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

1. Introduction to Application 2. Specific Aims 3. Background and Significance 4. Preliminary Studies/Progress Report 5. Research Design and Methods 6-12 13. Select Agent Research 14-17

Restructured Research Plan

1. Introduction to Application 2. Specific Aims

3. Research Strategy a. Significance b. Innovation c. Approach (incl. Preliminary Studies)

4-10 (renumbered) 11. Select Agent Research (Modified) 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 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

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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

measured.

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

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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

biomarkers.

We hypothesize that colon cancers can be more effectively detected using sensitive blood

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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

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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 work.

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 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 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

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Evidence of originality

③

Adequacy of scientific background

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Quality of research endeavors/publications to date

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Commitment to health-oriented research

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Need for further research experience and training

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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

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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?

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About HF Awards

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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 1 st and 2 nd 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