K99/ R00 Instructions

Component of Candidate Information

Eligibility

By the time of award, the individual must be a citizen or a non-citizen national of the United States or have been lawfully admitted for permanent residence (i.e., possess a currently valid Permanent Resident Card USCIS Form I-551, or other legal verification of such status), or for non-U.S. citizen/permanent residents the applicant U.S. institution for each phase of the application (K99 or R00) is responsible for determining and documenting in the application that the applicant investigator’s visa will allow him or her to remain in this country long enough to (a) transition to an independent research career in the U.S. during the proposed mentored (K99) phase and/or (b) be productive on the research project in the U.S. for the duration of the proposed independent research (R00) phase. Candidates must have a clinical or research doctorate and have no more than 5 years of postdoctoral research training at the time of application (resubmissions must also comply with this requirement). Back to Top

Formatting and Submission

Please use the following formatting guide to prepare your submission: Font- Use an Arial, Helvetica, Palatino Linotype, or Georgia typeface, a black font color, and a font size of 11 points or larger. (A Symbol font may be used to insert Greek letters or special characters; the font size requirement still applies.) Margins- Use standard paper size (8 ½” x 11). Use at least one-half inch margins (top, bottom, left, and right) for all pages. No information should appear in the margins, including the PI’s name and page numbers. Headers/ Footers- Please do not include page numbers, headers, or footers. These are added via the electronic Coeus System. Section Formatting- All top level documents (listed above in BOLD text) should be sent as separate documents in Word (.doc) and Adobe (.pdf) format to Christie Johnson, Research Service Analyst, INBT Back to Top

Title (80 characters max)

Enter a brief descriptive title of the project. Must be 80 characters or less. Back to Top

Cover Letter

The letter must include:

  • Application title
  • Funding Opportunity (PA or RFA) title of the NIH initiative.
  • List of referees (including name, department affiliation, and institution).
  • Request of an assignment (referral) to a particular awarding component (e.g. NIH IC) or Scientific Review Group (SRG). (The PHS makes the final determination.)
  • List of individuals (e.g., competitors) who should not review your application and why.
  • Disciplines involved, if multidisciplinary

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Project Narrative (3 Sentences Max)

Using no more than two or three sentences, describe the relevance of this research to public health. In this section, be succinct and use plain language that can be understood by a general, lay audience. Back to Top

Project Summary (30 Lines Max)/(Component of the Other Project Information Component)

This section must be no longer than 30 lines of text State the application’s broad, long-term objectives and specific aims, making reference to the health relatedness of the project (i.e., relevance to the mission of the agency). Describe concisely the research training program design and methods for achieving the stated goals. Back to Top

Specific Aims

Limited to one page. 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. Back to Top

Research Strategy

  • The candidate should describe his/her research that is relevant to the proposed R00 research plan. Ideally, this would include a brief description of research performed prior to the mentored phase, a description of the research planned during the mentored phase and a detailed description of the research planned for the independent phase. This narrative should describe what the candidate will accomplish during the mentored phase research that will enable him/her to launch an independent research program (i.e., what does the candidate still need to accomplish during the mentored phase in order to compete successfully once independence is achieved). It is anticipated that candidates will be best able to describe their current and past research.
  • The research description should demonstrate not only the quality of the candidate’s research thus far but also the novelty, significance, creativity and approach of the R00 phase research, as well as the ability of the candidate to carry out the research. Consequently, the research plan should provide a detailed rationale, experimental approach and plan for the independent phase research.
  • The application must also describe the relationship between the mentor’s research and the candidate’s proposed research plan. The application should describe how the candidate will gain independence from his/her mentors and achieve separation of his/her scientific research program from that of the mentor(s).
  • If more than one K99 phase mentor is proposed, the respective areas of expertise and responsibility should be described.
  • Data and Safety Monitoring (when applicable): Individual NIH institutes may have specific requirements for data and safety monitoring of clinical trials. Candidates proposing to conduct clinical trials should consult with relevant IC staff. Plans for data and safety monitoring must be included in research plans involving Phase I or Phase II clinical trials: Generally, this requirement may be satisfied in the submitted application by providing documentation that the sponsoring institution has an approved plan in place and providing a brief description of the key elements of the plan.

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Biographical Sketches for all Senior and Key Personnel

Limited to four pages Needed for Applicant, Sponsor, and Co Sponsor. Back to Top

Resource Sharing Plan

Generic version provided- Resource Sharing: All data obtained will be shared with the public openly via publication in the most rigorous, visible and appropriate scientific journals possible. Data will be published as soon as it is reasonable to do so (i.e., sufficient data generated to warrant a suitable paper). Supplemental data for each published paper will be made available in one location on the lab webpage of the PI related to this work. The PI and other investigators are open to collaboration with outside groups as well when there is mutual interest in this approach. In accordance to the NIH public access requirement (Section 218), we will submit to the National Library of Medicine’s PubMed Central an electronic version of our final peer-reviewed manuscripts upon acceptance for publication to be made publicly no later than 12 months after the official date of publication. We will make every effort to keep technologies developed as a result of this research project widely available and accessible to the research community. If patents are filed and the technology licensed, then we will seek first to achieve a non-exclusive license unless exclusivity is determined to be the best route for successful development of the technology for public use and benefit. We will seek a research exemption in order to preserve the right of the PI and other co-investigators, as well as the Johns Hopkins University’s right—and the right of other nonprofit organizations—to continue conducting non-commercial research with the licensed material or patented technology. Such exemption will preserve the right of Johns Hopkins University to use the materials, royalty-free, for teaching and research purposes and to sublicense other non-profits to use the materials for the same non-commercial uses.

Facilities

Identify the facilities to be used (Laboratory, Animal, Computer, Office, Clinical and Other). If appropriate, indicate their capacities, pertinent capabilities, relative proximity and extent of availability to the project. Describe only those resources that are directly applicable to the proposed work. Provide any information describing the Other Resources available to the project (e.g., machine shop, electronic shop) and the extent to which they would be available to the project. Back to Top

Equipment

List major items of equipment already available for this project and, if appropriate identify location and pertinent capabilities. Back to Top

Candidate’s Background (Component of Candidate Information)

  • Describe the candidate’s commitment to a career in a biomedical or behavioral research field relevant to the mission of one of the participating NIH ICs.
    • Describe the candidate’s potential to develop into a successful independent investigator.
    • Describe the candidate’s current as well as long-term research and career objectives.
    • If currently supported by an institutional or individual Ruth L. Kirschstein NRSA, describe the candidate’s current research training or fellowship program.
    • For individuals in postdoctoral positions with other titles although still in non-independent training positions, describe evidence of non-independence.

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    Career Goals and Objectives (Component of Candidate Information)

    • Present a systematic plan that: (1) shows a logical progression from the candidate’s prior research and training experiences to the training and research experiences proposed for the mentored phase of the award (K99) and subsequently to independent investigator status (R00); (2) justifies the need for further mentored career development to become an independent research investigator; and (3) that utilizes the relevant research and educational resources of the institution.
    • Candidates planning to be sponsored by an extramural institution should consult with the proposed mentor to discuss the proposed research training/career development plan for the mentored phase and the research plan to be presented in the application for the subsequent independent scientist phase.
    • If the candidate is planning an NIH intramural laboratory for the mentored phase, a mentor will need to be selected with whom the candidate can consult in preparing and submitting the application for the intramural mentored phase of the award. Individuals working at an NIH laboratory may work with their current mentor, or with another intramural investigator, provided the research experience proposed in this application will enhance the candidate’s scientific career.

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    Career Development/ Training Activities During Award Period (Component of Candidate Information)

    • Describe the career development plan and how it fits with the candidate’s goals and prior experience. A systematic plan should be presented for obtaining the necessary biomedical, behavioral, or clinical science background and research experience to launch an independent research career. The career development plan must be specifically tailored to meet the needs of the candidate and the ultimate goal of achieving independence as a researcher.
    • Describe the current training activities and how they relate to the career development plans and the career goals of the candidate. Candidates must justify the need for the award, both the mentored phase and the independent scientist phase, and must provide a convincing case that the proposed period of support (1-2 years as a mentored candidate followed by up to 3 years as an independent scientist) will substantially enhance his/her career and/or will allow the pursuit of a novel or promising approach to a particular research problem.
    • The candidate should describe how the career development plan will promote the candidate’s success and scientific independence. This plan should describe activities such as those that will lead to new and/or enhanced research, grant-writing, communication and laboratory management skills and knowledge. The candidate should also describe how these skills will contribute to research productivity and facilitate the development of new approaches and directions for investigation. Courses or other activities that might allow the candidate to expand the scope of his/her research in order to improve the potential for success in gaining further independent funding are particularly encouraged.
    • The candidate must describe the plan for evaluation of his/her progress during the mentored phase and for the transition to the independent phase.
    • The candidate and K99 phase mentor (see below) must describe plans for the transition to the independent phase.

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    Training in the Responsible Conduct of Research

    • Applications must include a plan to obtain instruction in the responsible conduct of research.
    • This section should document prior instruction in responsible conduct of research during the applicant’s current career stage (including the date of last occurrence) and propose plans to receive instruction in responsible conduct of research.
    • Such plans must address five instructional components, format, subject matter, faculty participation, duration of instruction, and frequency of instruction, as outlined and explained in NOT-OD-10-019.
    • The plan may include career stage-appropriate, individualized instruction or independent scholarly activities that will enhance the applicant’s understanding of ethical issues related to their specific research activities and the societal impact of that research.
    • The role of the sponsor/mentor in responsible conduct of research instruction must be described. Applications lacking a plan for instruction in responsible conduct of research will be considered incomplete and may be delayed in the review process or may not be reviewed.
    • The background, rationale and more detail about instruction in the responsible conduct of research can be found in NOT-OD-10-019.

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    Statements by Mentor, Co-mentor(s), Consultants, Contributors (Component of Statements of Support)

    • The candidate must name a primary mentor (sponsor), who, together with the candidate, is responsible for the planning, direction, and execution of the K99 phase program. The candidate may also identify co-mentors as appropriate to the goals of the program.
    • The primary mentor should be recognized as an accomplished investigator in the proposed research area and have a track record of success in training individuals in postdoctoral positions who have gone on to become independent investigators.
    • The mentor should have sufficient independent research support to cover the costs of the proposed research project in excess of the allowable costs of this award.
    • The application must include a statement from the mentor(s) that provides: 1) information on their research qualifications and previous experience as a research supervisor; 2) a plan that describes the nature of the supervision and mentoring that will occur during the proposed award period, including how the candidate’s scientific and professional independence will be promoted; 3) a description of the elements of the planned research training, including any formal course-work; and 4) a plan for transitioning the candidate from the mentored phase to the independent scientist phase of the award.
    • Similar information must be provided by any co-mentor. If more than one mentor is proposed, the respective areas of expertise and responsibility of each should be described. Co-mentors should describe clearly how they will coordinate with the primary mentor and the candidate.
    • The mentor must agree to provide annual evaluations of the candidate’s progress for the initial mentored phase as required in the annual progress report.
    • The mentor must agree to review and comment on the extramural independent scientist (R00) phase application (See Section below on Activating the Independent Phase of the Pathway to Independence Award (R00).
    • Consultant(s)/Collaborator(s): Signed statements must be provided by each consultant/collaborator confirming their participation in the project and describing their specific roles. Collaborators and consultants generally do not need to provide their biographical sketches. However, information should be provided clearly documenting the appropriate expertise in the proposed areas of consulting/collaboration. Collaborators/consultants are generally not directly involved in the development of the career of the candidate as an independent investigator.

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    Description of Institutional Environment (Component of Environment and Institutional Commitment to the Candidate)

    • The sponsoring institution must document a strong, well-established research and career development program related to the candidate’s area of interest, including a high-quality research environment with key faculty members and other investigators capable of productive collaboration with the candidate.
    • Describe the sponsoring institution’s scientific environment including the resources and facilities that will be available to the candidate.
    • Describe how the institutional research environment is particularly suited for the development of the candidate’s research career and the pursuit of the proposed research plan and progression to the R00 phase.

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    Institutional Commitment to the Candidate’s Research Career Development (Component of Environment and Institutional Commitment to the Candidate)

    • The sponsoring institution must provide a statement of commitment to the candidate’s development into a productive, independent investigator and to meeting the requirements of this award. It should be clear that the institutional commitment to the candidate is not contingent upon receipt of the K99/R00 award.
    • Provide assurances that the candidate will be able to devote a minimum of 9 person-months (75% of full-time professional effort) to the development of their research program. The remaining effort should be devoted to activities related to the development of the candidate’s career as an independent scientist.
    • Provide assurance that the research facilities, resources, and training opportunities, including faculty capable of productive collaboration with the candidate, will be available for the candidate’s planned career development and research programs.
    • Provide appropriate time and support for any proposed mentor(s) and/or other staff consistent with the career development plan.
    • If the candidate is not a U.S. Citizen or permanent resident, the sponsoring institution must include information about their visa status and an assurance that the candidate’s visa provide sufficient time to complete both phases of the K99/R00 award at a U.S. Institution.

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    Letters of Reference – Letters of Reference are due by the application receipt deadline date.

    Candidates must carefully follow the SF424 (R&R) Application Guide, including the time period for when letters of reference will be accepted Applications lacking the required reference letters will not be reviewed (see: NOT-OD-11-036). Please note that the specified format must be used. This is a separate process from submitting an application electronically. Reference letters are submitted directly through the eRA Commons Referee Information link and not through Grants.gov. Back to Top

    Literature Cited

    Provide a bibliography of any references cited in the application. Each reference must include the names of all authors (in the same sequence in which they appear in the publication), the article and journal title, book title, volume number, page numbers, and year of publication. Include only bibliographic citations. Applicants should be especially careful to follow scholarly practices in providing citations for source materials relied upon when preparing any section of the application. Back to Top

    Compliance Questionnaire – Appendix B

    This must be completed for all grant submissions. Although this form is an internal document it provides PI answers to sponsor specific questions. Please complete and return. This link will download the most current version of the form from the Research Projects Administration Office. Back to Top

    Protection of Human Subjects (Please see the Appendix C)

    Women and Minorities (explanation)

    In this section of the Research Training Plan, address, at a minimum, the following four points: 1. The targeted/planned distribution of subjects by sex/gender and racial/ethnic groups for each proposed study or protocol using the format in the Targeted/Planned Enrollment Table (example below). If using existing specimens and/or data without access to information on the distribution of women and minorities, so state and explain the impact on the goals of the research as part of the rationale that inclusion cannot be described. Alternatively, describe the gender and minority composition of the population base from whom the specimens and/or data will be obtained. Include the Targeted/Planned Enrollment Tables in this section. 2. A description of the subject selection criteria and rationale for selection of sex/gender and racial/ethnic group members in terms of the scientific objectives and proposed study design. The description may include, but is not limited to, information on the population characteristics of the disease or condition under study. 3. A compelling rationale for proposed exclusion of any sex/gender or racial/ethnic group (see examples below). 4. A description of proposed outreach programs for recruiting sex/gender and racial/ethnic group members as subjects. Below are examples of acceptable justifications for the exclusion of: A. One gender: 1. One gender is excluded from the study because: • Inclusion of these individuals would be inappropriate with respect to their health; • The research question addressed is relevant to only one gender; • Evidence from prior research strongly demonstrates no difference between genders; or • Sufficient data already exist with regard to the outcome of comparable studies in the excluded gender, and duplication is not needed in this study. 2. One gender is excluded or severely limited because the purpose of the research constrains the applicant’s selection of study subjects by gender (e.g., uniquely valuable stored specimens or existing datasets are single gender; very small numbers of subjects are involved; or overriding factors dictate selection of subjects, such as matching of transplant recipients, or availability of rare surgical specimens). 3. Gender representation of specimens or existing datasets cannot be accurately determined (e.g., pooled blood samples, stored specimens, or data-sets with incomplete gender documentation are used), and this does not compromise the scientific objectives of the research. B. Minority groups or subgroups: 1. Some or all minority groups or subgroups are excluded from the study because: • Inclusion of these individuals would be inappropriate with respect to their health; • The research question addressed is relevant to only one racial or ethnic group; • Evidence from prior research strongly demonstrates no differences between racial or ethnic groups on the outcome variables; • A single minority group study is proposed to fill a research gap; or • Sufficient data already exists with regard to the outcome of comparable studies in the excluded racial or ethnic groups and duplication is not needed in this study. 2. Some minority groups or subgroups are excluded or poorly represented because the geographical location of the study has only limited numbers of these minority groups who would be eligible for the study, and the investigator has satisfactorily addressed this issue in terms of: • The size of the study; • The relevant characteristics of the disease, disorder or condition; or • The feasibility of making a collaboration or consortium or other arrangements to include representation. 3. Some minority groups or subgroups are excluded or poorly represented because the purpose of the research constrains the applicant’s selection of study subjects by race or ethnicity (e.g., uniquely valuable cohorts, stored specimens or existing datasets are of limited minority representation, very small numbers of subjects are involved, or overriding factors dictate selection of subjects, such as matching of transplant recipients or availability of rare surgical specimens). 4. Racial or ethnic origin of specimens or existing datasets cannot be accurately determined (e.g., pooled blood samples, stored specimens or data sets with incomplete racial or ethnic documentation are used) and this does not compromise the scientific objectives of the research. Back to Top

    Targeted/ Planned Enrollment Table

    Form: Targeted/ Planned Enrollment Table • Provide the study title. • The “Total Planned Enrollment” means the number of subjects that are expected to be enrolled in the study, consistent with the definition in ClinicalTrials.gov. • The “Total Planned Enrollment” will be reported in two ways in the table: by “Ethnic Category” and by “Racial Categories.” • “Ethnic Category”: Provide the numeric distribution of the Total Planned Enrollment according to ethnicity and sex/gender in the top part of the table. • “Racial Categories”: Provide the numeric distribution of the Total Planned Enrollment, this time by racial categories and sex/gender, in the bottom part of the table. Note that Hispanic is an ethnic, not a racial, category. • If there is more than one study/protocol, provide a separate table for each. Back to Top

    Inclusion of Children

    • Provide either a description of the plans to include children, or, if children will be excluded from the proposed research, application, or proposal, present an acceptable justification for the exclusion (see below). • If children are included, the description of the plan should include a rationale for selecting a specific age range of children. The plan also must include a description of the expertise of the investigative team for working with children at the ages included, of the appropriateness of the available facilities to accommodate the children, and the inclusion of a sufficient number of children to contribute to a meaningful analysis relative to the purpose of the study. • Scientific Review Groups will assess each application as being acceptable or unacceptable with regard to the age-appropriate inclusion or exclusion of children in the proposed research project. • When children are involved in research, the Additional Protections for Children Involved as Subjects in Research (45 CFR part 46 Subpart D) apply and must be addressed under the Protections Against Risk subheading (4.1.2.b). Justifications for Exclusion of Children For the purposes of this policy, all individuals under 21 are considered children; however, exclusion of any specific age group, such as individuals under 18, should be justified in this section. It is expected that children will be included in all clinical research unless one or more of the following exclusionary circumstances apply: 1. The research topic to be studied is not relevant to children. 2. Laws or regulations bar the inclusion of children in the research. 3. The knowledge being sought in the research is already available for children or will be obtained from another ongoing study, and an additional study will be needlessly redundant. Documentation of other studies justifying the exclusions should be provided. NIH program staff can be contacted for guidance on this issue if the information is not readily available. 4. A separate, age-specific study in children is warranted and preferable. Examples include: a. The condition is relatively rare in children, as compared to adults (in that extraordinary effort would be needed to include children, although in rare diseases or disorders where the applicant has made a particular effort to assemble an adult population, the same effort would be expected to assemble a similar child population with the rare condition); or b. The number of children is limited because the majority are already accessed by a nationwide pediatric disease research network; or c. Issues of study design preclude direct applicability of hypotheses and/or interventions to both adults and children (including different cognitive, developmental, or disease stages or different age-related metabolic processes). While this situation may represent a justification for excluding children in some instances, consideration should be given to taking these differences into account in the study design and expanding the hypotheses tested, or the interventions planned, to allow inclusion of children rather than excluding them. 5. Insufficient data are available in adults to judge potential risk in children (in which case one of the research objectives could be to obtain sufficient adult data to make this judgment). Although children usually should not be the initial group to be involved in research studies, in some instances, the nature and seriousness of the illness may warrant their participation earlier based on careful risk and benefit analysis. 6. Study designs are aimed at collecting additional data on pre-enrolled adult study subjects (e.g., longitudinal follow-up studies that did not include data on children). 7. Other special cases can be justified by the investigator and found acceptable to the review group and the Institute/Center Director. Back to Top

    Vertebrate Animals

    If Vertebrate Animals are involved in the project, address each of the five points:

    1. Provide a detailed description of the proposed use of the animals in the work outlined in the “Research Strategy” section. Identify the species, strains, ages, sex, and numbers of animals to be used in the proposed work.
    1. Justify the use of animals, the choice of species, and the numbers to be used. If animals are in short supply, costly, or to be used in large numbers, provide an additional rationale for their selection and numbers.
    1. Provide information on the veterinary care of the animals involved.
    1. Describe the procedures for ensuring that discomfort, distress, pain, and injury will be limited to that which is unavoidable in the conduct of scientifically sound research. Describe the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices, where appropriate, to minimize discomfort, distress, pain, and injury.
    1. Describe any method of euthanasia to be used and the reasons for its selection. State whether this method is consistent with the recommendations of the Panel on Euthanasia of the American Veterinary Medical Association (AVMA) Guidelines on Euthanasia. If not, present a justification for not following the recommendations. Do not use the vertebrate animal section to circumvent the page limits of the Research Strategy.

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    Select Agent Research

    Select agents are hazardous biological agents and toxins that have been identified by DHHS or USDA as having the potential to pose a severe threat to public health and safety, to animal and plant health, or to animal and plant products. CDC and select agents registry maintain a list of these agents. See Select Agent and Toxins List. This also includes listings for exemptions. If any of the activities proposed in your application involve the use of select agents at any time during the proposed project period, either at the applicant organization or at any other performance site, address the following three points for each site at which select agent research will take place. Although no specific page limitation applies to this section, be succinct.

    1. Identify the select agent(s) to be used in the proposed research.
    2. Provide the registration status of all entities* where select agent(s) will be used.
      • If the performance site(s) is a foreign institution, provide the name(s) of the country or countries where select agent research will be performed.
    3. Provide a description of all facilities where the select agent(s) will be used.
      • Describe the procedures that will be used to monitor possession, use and transfer of select agent(s).
      • Describe plans for appropriate biosafety, biocontainment, and security of the select agent(s).

    Back to Top Appendix A (Table of Page Limits) Appendix B (Compliance Questionnaire) Appendix C (Human Subjects- Information & Training)