Isidro B. Salusky, MD Distinguished Professor of Pediatrics Division Chief, Pediatric Nephrology

Director, Clinical Translational Research Center Associate Dean for Clinical Research

David Geffen School of Medicine at UCLA

• Intensive, supervised research experience in the fields of biomedical and behavioral research, including translational research

• Participating ICs vary in programmatic and budgetary specifics, and in size and duration of awards

• Candidate must devote a minimum of 9 person months (75% of full-time professional effort) to specified research plan

• In general, candidates can request 3-5 years, depending on individual needs to achieve research independence

• Awards are not renewable and are not transferable from one PI to another

• Not all ICs utilize the K08 so prospective applicants should contact the relevant NIH staff for IC-specific information on restrictions

• Electronic template system (UCLA Cayuse) for online fill-in of Cover Components and other SF 424 “form pages,” e.g., institutional and candidate information, other senior/key personnel, project/performance site locations, budget data, Checklist

• Project Summary/Abstract: Candidate, Environment, and Research (1 page maximum, including the candidate's immediate and long-term career goals, key elements of the research career development plan, and description of the research project)

• Project Narrative (Relevance Statement, 2-3 sentences, no jargon) • Facilities and Other Resources: Documentation of key resources

for the proposed research, training, career development

• Specific Aims (1 page) • Career Development Plan Sections: Candidate's Background, Career

Goals, and Objectives; Career Development/Training Activities during Award Period; Training in the Responsible Conduct of Research + Research Strategy Sections: Significance, Innovation, Approach = 12 pages total (including figures, tables, graphs, etc.)

• Bibliography and Literature Cited • Human Subjects Sections: Protection of Human Subjects, Inclusion of

Women and Minorities, Targeted/Planned Enrollment Table, Inclusion of Children

• Other Research Plan Sections: Vertebrate Animals, Select Agent Research, Consortium/Contractual Arrangements, Resource Sharing Plan

• Cover Letter (obligatory) • Letters of Reference (minimum 3, maximum 5): due

by the application receipt deadline date • Statements of Support from Mentor, Co-Mentors,

Consultants, Contributors • Appendix (optional)

SPECIAL REQUIREMENT: Mentor(s)

• Applicant must name a primary sponsor/mentor, who together with the candidate is responsible for the planning, direction, and execution of the career development program.

• The mentor should be recognized as an accomplished investigator in the proposed program and have a track record of success in training similar investigators.

• The mentor should have sufficient independent support to cover the costs of the proposed project in excess of the allowable costs of this award.

• Candidates may also nominate co-mentors as appropriate to the goals of the specified research program.

• Experience • Availability • Interest to work • Track record with previous mentees

• Adequate resources: grant support • The choice of one or two senior scientists is the single

most important decision

SPECIAL REQUIREMENT: Institutional Environment

• Demonstrate your institution’s strong, well-established record of career development activities and faculty qualified in biomedical, behavioral, or clinical-translational research to serve as mentors. (CTSI award if available)

• Demonstrate the institution’s commitment to your development as a productive investigator and willingness to allow the protected time needed to complete your career development program .

• Describe a career development program that will maximize the use of this environment, including available facilities and resources.

Candidate’s Background

• Describe your commitment to an academic career in patient-oriented research for the K23 OR biomedical/behavioral research for the K08.

• Describe your professional responsibilities in the grantee institution and elsewhere and show their relation to the proposed activities on the career award.

• Present evidence of your ability to interact and collaborate with other scientists.

• Describe prior training and how it relates to your objectives and long-term career plans.

Candidate’s Background (cont.)

• Describe your research efforts to this point in your research career, including publications and prior research interests and experience.

• Provide evidence of your potential to develop into an independent investigator.

• Include a statement that you will commit at least 9 person-months (75% of full-time professional effort) to the research program and related career development activities. The mentor or department chair must agree and provide a statement in the application documenting that this percentage of your time will be protected.

Career Development/Training Activities

• You and your mentor(s) are jointly responsible for the preparation of the Career Development Plan. A timeline is often helpful. The sponsor/mentor may form an advisory committee to assist with the development of the program of study or to monitor your progress through the career development program.

• The didactic (if any) and the research aspects of the plan must be designed to develop the necessary knowledge and research skills in scientific areas relevant to your career goals. You must demonstrate you have received training or will participate in courses such as data management, epidemiology, study design (including statistics), hypothesis development, drug development, as well as the legal and ethical issues associated with research on human subjects.

• Describe your professional responsibilities/activities, including other research projects, beyond the minimum required 75% effort commitment to the K award. Explain how these responsibilities/activities will help ensure career progression to achieve independence as an investigator.

• Specific Aims 1

• First three items of Candidate Information (Candidate's Background, Career Goals and Objectives, and Career Development/Training Activities During Award Period and Research Strategy 12 (for all sections combined)

• Training in the Responsible Conduct of Research 1

• Statements by Mentor, Co-Mentors, Consultants, Contributors 6 • Description of Institutional Environment 1 • Institutional Commitment to Candidate’s Research Career Development 1 • Biographical Sketch 4

Specific Aims and Research Strategy sections follow the R01 model:

– SPECIFIC AIMS (1 page) •What do you intend to do?

– RESEARCH STRATEGY (12 pages, including Career Development Plan) – Significance

•What has already been done in the field(s) and why is the proposed project important in the context of prior work?

– Innovation •What is novel about the proposed project and how will it advance the field(s)?

– Approach •How are you going to achieve the specific aims of the project?

• One page limit

• One paragraph introduction to the topic: Broad enough to provide background information yet narrow enough to provide focus for the project

• 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

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

• Focus and rewrite/hone

• Explain the importance of the problem or critical barrier to progress in the field that the proposed project addresses.

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

• Describe how the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field will be changed if the proposed aims are achieved.

• Outline the background for the current proposal

• Critically evaluate current knowledge – Supporting information – Conflicting information – Your own data, if available

• Identify gaps in existing knowledge that the project will fill

• Link to specific aims or hypotheses • Link to broader, long-term objectives

• Outline the background – Not a general review – Select salient features and focus on key issues – Provide perspective – Develop concepts

• Evaluate current knowledge

– Consider conflicting views and acknowledge work that has already been done

– Be knowledgeable – Be diplomatic – Be precise

• Identify key areas where information is missing and innovation is needed to fill knowledge gaps – Focus the attention of the reviewer

• Make it interesting • Sell the product

– Provide new information, either your own or others – Offer new perspectives

• Describe how the specific aims or hypotheses will fill gaps in our current knowledge

• Together, Specific Aims, Significance, and Innovation should provide an integrated and compelling justification for the project

• Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project. Unless addressed separately in the Resource Sharing Plan, include how the data will be collected, analyzed, and interpreted as well as any resource sharing plans as appropriate.

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

• 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.

• Point out any procedures, situations, or materials that may be hazardous to personnel and precautions to be exercised. A full discussion on the use of select agents should be included in the Select Agents Research section of the application.

• Describe the work to be done to – Address each specific aim – Test each hypothesis

• Outline how each study or experiment will address the specific aims or hypotheses described previously

• Organization is important • Follow a logical sequence • Describe methods to be used

– General (overview) • Study design • Lab procedures • Statistical procedures • Justify

– Specific studies or experiments • Technical / methodological issues • Document

General Methods • Clinical project

– Measurement instruments – Study population – Recruitment – Longitudinal follow-up

• Laboratory project – Cell or tissue culture methods – Specific analytical procedures

• Precision and accuracy of methods • Previous experience

Experimental Procedures • Describe experiments in sufficient detail

– How they are done – Data to be obtained – How data are analyzed – Results expected – Conclusions reached

• Expected findings • Unexpected findings • Alternative interpretations • Additional studies

• Relate results and interpretation to specific aims / hypotheses

Experimental Procedures • To address Specific Aim #1

– Experiment #1 – Experiment #2

• To address Specific Aim #2

– Experiment #3 – Experiment #4 – Experiment #5

Experimental Procedures • To address Specific Aim #1

– Experiment #1 • Procedure • Analysis / interpretation

• Can this person do the work?

– Proven methods – Technical expertise – Resources available – Study population

• Access • Follow-up

– Background and experience – Publications – Collaborators

• Propose a research project that is consistent with your level of research development and objectives of your career development. The research description should demonstrate not only the quality of your research thus far but also the novelty, significance, creativity, and approach, as well as your ability to carry out the research.

• While the focus of the K23 award is patient-oriented research, complementary laboratory research directly related to patient-oriented research may be proposed in the application, thereby providing an opportunity for a career development experience in translational research.

• The application must also describe the relationship between your mentor’s research and your proposed research plan.

• If more than one mentor is proposed, their respective areas of expertise and responsibility should be described.

Statements by Mentor and Any Co-Mentors •The application must include a statement from the mentor, providing (1) information on his/her research qualifications and previous experience as a research supervisor

(2) a plan that describes the nature of the direct supervision and mentoring that will occur during the proposed award period, as aligned with the Research Strategy

(3) a plan for your career progression to move from the mentored stage to independent research investigator status during the project period of the award, including identification of aspects of the proposed research that you will be able to take into your independent position

(4) a plan for monitoring your research, publications, and progression toward independence

(5) documentation of the availability of sufficient research support and facilities for high-quality research

(6) description of courses, seminars, and opportunities for interaction with other scientists and trainees, including training in career skills such as grant writing and effective presentations

Statements by Mentor and Any Co-Mentors (cont.)

•Similar information must be provided by any co-mentor (s). If more than one co-mentor is proposed, the respective areas of expertise and responsibility of each should be described. Co-mentors should clearly describe how they will coordinate the mentoring of the candidate. If any of the co-mentors are not located at the home institution, a statement regarding the modes and frequency of communication with you should be provided.

•The primary mentor must agree to provide annual evaluations of your progress as required in the annual progress report.

Statement by Consultants and/or Contributors

• Signed statements must be provided by each consultant/collaborator, confirming participation in the project and describing their specific roles.

• Collaborators and consultants do not need to provide biographical sketches, but each must clearly document 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.

Data and Safety Monitoring Plan (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.

• A plan for data and safety monitoring must be included in research plans involving phase I or phase II clinical trials. In general, this requirement may be satisfied in the 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.

• Electronic submission of reference letters is a separate process from submitting an application electronically. Reference letters are submitted directly by the referees through the eRA Commons; must be submitted NO LATER THAN application submission due date.

• You must arrange to have at least 3 (but no more than 5) letters of reference submitted on your behalf. The letters should be from well-established scientists (referees) and should address your qualifications and competence as well as your potential for becoming an independent investigator. These letters should be from individuals not directly involved in the application, but who are familiar with your educational background, training, and interests.

• Applications that are missing the required letters of reference may be delayed in the review process or not accepted.

Description of Institutional Environment •Document a strong, well-established, high-quality research and career development environment related to your area of interest, including key faculty members and other investigators capable of productive collaboration with you.

•Describe how the institutional research environment is particularly suited for the development of your research career and the pursuit of the proposed research plan.

•Describe the resources and facilities that will be available to you, including the UCLA CTSI Clinical Translational Research Center (CTRC).

Institutional Commitment to Candidate’s Research Career Development • Institution (e.g., department chair) must provide a statement of commitment to your

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 on receipt of this career award.

•Provide assurances that you will be able to devote a minimum of 9 person-months (75% of full-time professional effort) to the fulfillment of the career development program. The remaining effort should be devoted to activities related to the development of your career as an independent clinician scientist, e.g., clinic responsibilities, teaching, and/or additional research activities.

•Provide assurances that you will be provided with appropriate office and laboratory

space, equipment, and other resources and facilities (including access to clinical and/or other research populations) to carry out the proposed career development plan.

Institutional Commitment to Candidate’s Research Career Development •Provide appropriate time and support for any proposed mentor(s) and/or other staff

consistent with the career development plan. • If you will be using CTSI resources (letter Dr Dubinett) and/or specific aspects of CTSI

such as CTRC during the course of the award, include a letter of agreement from the CTRC Program Director (Dr Salusky) as part of the application.