NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this funding opportunity announcement (FOA) is to invite applications to participate in the Clinical and Translational Science Award (CTSA) program, which supports high quality translational and clinical research locally, regionally, and nationally, and fosters innovation in research methods, training, and career development.

Translating biomedical discoveries into clinical applications that improve human health is a complex process with high costs and substantial failure rates. This can result in a delay of years or decades before discoveries in biomedical research result in health benefits for patients and communities. Recognizing the need to improve translation, the National Institutes of Health (NIH) established the CTSA Program in 2006. In 2011, the CTSA Program became part of the National Center for Advancing Translational Sciences (NCATS). NCATS' mission is to identify and instantiate the general scientific and operational principles underlying each step of the translational continuum, thus transforming translation from an empirical process to a predictive science. To accomplish this, NCATS supports research to identify and test promising translational innovations and develop, demonstrate, and disseminate advances across the translational science spectrum.

In 2012, at the suggestion of Congress, the Institute of Medicine (IOM) was invited to assess the CTSA Program and make recommendations to enhance its effectiveness in meeting the NCATS mission. In 2013, the IOM delivered its report, suggesting among other recommendations that the program could greatly increase its impact if the multiple largely independent CTSA Program units were to evolve into a national network to enhance the transit of therapeutic, diagnostic, and preventive interventions along the developmental pipeline; disseminate innovative translational research methods and best practices; and provide leadership in informatics standards and policy development to promote shared resources . Unless otherwise indicated, quotes in this FOA are from this IOM report, which can be found at "The CTSA Program at NIH: Opportunities for Advancing Clinical and Translational Research - Institute of Medicine".

Based on these recommendations and input from an NCATS Advisory Council Working Group (https://ncats.nih.gov/files/CTSA-IOM-WG-report-5-2014.pdf), NCATS developed the following goals for the CTSA Program in an ideal state.

1. Workforce Development - The translational science workforce has the skills and knowledge necessary to advance translation of discoveries.

2. Collaboration/Engagement - Stakeholders are engaged in collaborations to advance translation.

3. Integration - Translational science is integrated across its multiple phases and disciplines within complex populations and across the individual lifespan.

4. Methods/Processes - The scientific study of the process of conducting translational science itself enables significant advances in translation.

5. Informatics Innovative informatics solutions are used to advance translational research, train the CTSA workforce, disseminate best practices, engage communities of the stakeholders, and integrate clinical and basic research data.

With the goal of catalyzing the development of methods and technologies that lead to more efficient translation of biomedical discoveries into interventions shown to improve health, NCATS is evolving the CTSA Program into an integrated research and training environment for clinical and translational sciences that aims to dramatically improve efficiency and quality across the translational research spectrum.

To meet the particular training and career development needs of translational science, NCATS encourages innovative research training and career development programs that impart the knowledge, skills, and attitudes particular to translational science. CTSA education programs should, e.g., provide training in rigorous research methodologies, elimination of bias in experimental design and reporting, and knowledge of regulatory sciences and entrepreneurship. Opportunities for trainees to gain direct experience with parts of the translational ecosystem outside academia are also important, such as research externships in industry, regulatory agencies, nonprofit patient-advocacy groups, or other CTSA Program hubs with strengths different from their home hub. With an increased focus on core competencies in translational research, in addition to formal degrees, the CTSA Program training and career development programs should provide flexibility to adapt to individual training needs. Pursuant to the IOM report, the CTSA Program should promote diversity in the translational science workforce. CTSA Program Hubs are encouraged to collaborate with each other in education and training initiatives. Taking advantage of modern information technology, CTSA Program hubs should share methods and online resources, and disseminate tools and approaches. The NCATS' mission is to conduct and support research, training, health information dissemination, and other programs with respect to translational science. This funding opportunity seeks to facilitate the training of scholars from diverse backgrounds underrepresented in translational science who are knowledgeable about and available to focus on translational science later in their careers.

This FOA defines a set of overarching strategic goals for the CTSA Program to which each of the CTSA Program hubs should contribute. The FOA also defines a set of standards and resources that should be available at each CTSA Program hub to allow the CTSA Program to function as a flexible research network. The medical centers that make up the CTSA network are referred to as CTSA Program hubs to indicate their central role in their local environments where they coordinate and collaborate with multiple spokes (e.g. hospitals, clinics). An important operational principle of all NCATS programs, including the CTSA Program, is to maximize impact via a catalytic approach: developing, demonstrating utility of, and then disseminating improvements in translational science and operations. Depending on the problem being addressed, CTSA Program hubs are expected to develop and demonstrate solutions to translational roadblocks individually, as groups of hubs, or as a network whole; in all cases, dissemination of successful solutions throughout the network, and to the translational research community as a whole, is an explicit goal and expectation.

The NCATS CTSA Program, as a whole, supports the full spectrum of clinical and translational research. The CTSA Program hubs are a critical part of the program. Given the enormous variety of translational scientific and operational issues in need of effective solutions, and the rich diversity of academic medical institutions, each hub is both required to have certain common capacities and is encouraged beyond these to bring its own unique strengths to the program and the network. Defined sets of capacities and resources should be present at each hub so that it can act as a qualified partner in the CTSA Program, promoting an environment of quality, safety and efficiency for translational and clinical research. CTSA Program Hubs should be agents of continuous improvement as they identify gaps and opportunities in the research process and develop and instantiate innovative solutions at their institutions. In training and operations, CTSA Program Hubs should promote the team science required for translational research, and the development and nurturing of the translational research workforce.

An additional important objective for each CTSA Program Hub is the support of collaboration among CTSA Program Hubs towards building a national CTSA network. This national network will allow for the efficient planning and implementation of high-quality multi-center research, will harmonize standards and best practices, will enhance translational research training through sharing curricula and online training modules/courses when appropriate, and will provide opportunities for unique research training and career development opportunities, both within and outside of the CTSA Program Hub. Synergy within the CTSA Program is likely to yield greater impact than any sum of unique, individual efforts. Strengthening synergy adds to the justification of the nation’s investment into the CTSA Program.

Enhancing the CTSA Program’s capacity as a network requires changes at the local hubs. It is expected that these changes will improve the local hubs ability to compete nationally and internationally, and will increase scientific and economic opportunities. Evolution of the CTSA Program into a synergistic network will benefit all participants, and most importantly result in improved public health with individuals enjoying more effective prevention, diagnosis and treatment of diseases sooner.

NCATS has issued four additional FOAs to strengthen the CTSA Program’s network capacity.

RFA-TR-15-002: To create new Trial Innovation Centers (TICs) that will focus on multi-site clinical studies through centralized infrastructure [such as central Institutional Review Boards (IRBs) and streamlined subcontracting]

RFA-TR-15-004: To create new Recruitment Innovation Centers (RICs) to use innovative informatics tools in trial planning by providing site-specific de-identified counts of potential trial participants meeting entry criteria and to assist investigators in recruitment efforts.

PAR-15-172 / PAR-15-173: To encourage innovative collaborative work among three or more CTSA Program Hubs.

NCATS expects that all CTSA Program Hubs will work with the TICs and RICs.

This FOA calls for applications from medical research institutions to participate as hubs in the CTSA Program. Each application consists of 2-3 parts which are linked at the time of application, but will be separated at the time of award:

• UL1 award for a translational science hub that provides A. Administrative Core; B. Informatics; C. Community and Collaboration; D. Translational Endeavors; E. Research Methods; F. Hub Resource Capacity; G. Network Capacity; and H. Optional Functions. A through G are required parts of the application, and H is optional.
• KL2 award for institutional career development core (I. Inst Career Dev Core);
• TL1 award (optional) to support research training for pre- and post-doctorates [J. National Research Service Award (NRSA) Training Core].

The UL1 will receive one score encompassing all functions (A-H). The KL2 and TL1 components will be reviewed by training and career development experts and will receive separate scores. The overall impact score for the U54 will include the balance of all components. When NCATS issues the separate yet linked KL2 and/or TL1 awards, it will formally designate as PD/PIs those individuals identified with the Project Role of Other-Project Lead KL2 and/or TL1 in the application. Meritorious KL2 and TL1 awards will only be made when the associated UL1 is funded. Thus, awarding a CTSA Program Hub might include a UL1 alone; UL1 and KL2; UL1 and TL1; or UL1, KL2 and TL2. The UL1, KL2, and TL1 awards will each maintain their own, separate budgets.

CTSA Program Hubs should innovate research training and career development, and may include non-degree opportunities tailored to the specific needs of the workforce at the CTSA Program Hub. The CTSA TL1 and KL2 programs are complementary and focus on the education of pre- and postdoctoral trainees, and on the career development of early-career translational researchers, respectively.

In addition, the CTSA Program Hubs contribute to the continuing education of the members of the clinical and translational research team so that they have mastered core competencies in their own discipline, and sufficient knowledge of other disciplines to confer the capacity to effectively communicate and collaborate as members of multidisciplinary teams. For study personnel engaged in NIH funded clinical trials, continuing education should include Good Clinical Practice (GCP) training as a minimum standard (https://ncats.nih.gov/files/gcp-training.pdf). CTSA Program Hubs should advance team science and develop academic promotion criteria that help create a viable career path for translational scientists.

Translational science is a team-based endeavor. CTSA Program Hubs are expected to support active partnerships throughout the translational process. To accelerate discovery, these partnerships should be formed not only between academic collaborators focused on different disciplines in translational science, but also by involving, where and when appropriate, other stakeholders and communities, such as patients, their caregivers and families (local and online communities), non-profit organizations, governmental agencies, community-based clinicians (hospitals, practices, and clinics), health care delivery systems, industry, and other entities. CTSA Program Hubs should develop a methodological framework for discovering, demonstrating and disseminating successful collaboration models.

Translational research must study not only aggregate populations, but also focus on subpopulations with distinct characteristics, including, e.g., the young and old, to uncover the interrelationships of disease phenotype with genomics, environmental exposures, health-related behaviors, and social factors across the lifespan. CTSA Program Hubs should have plans to enhance the participation in research of pediatric, geriatric, and other special populations, and in some instances, make them the focus of study. CTSA Program Hubs should aim to include underserved populations, address health disparities, and approach cultural factors as a variable to be examined when developing translational innovations. Approaches could, e.g., include designating a point person at the hub for research in these special populations, as appropriate for the individual program strengths and interests. CTSA Program Hubs should seek to implement methodological innovations to integrate special populations into translational research.

CTSA Program Hubs are expected to develop, demonstrate, and then disseminate solutions to roadblocks to the efficiency and effectiveness of clinical and translational research. Specifically, in response to this FOA, applicants should include plans for the development of tools and methods that improve the translational process, and if successful, their demonstration across the CTSA Program Hub, and later their dissemination across the CTSA networks. Plans should be included to promote a research-friendly environment where patients, clinicians and other stakeholders are given easily accessible opportunities to contribute to research and where the environment facilitates the rapid integration of advances in translational research into health care. In addition, the application should include plans for adoption and implementation of innovative policies and infrastructure that improve the quality of human subject protections and promote a culture of responsibility, while streamlining institutional bureaucracy, decreasing investigator burden, and measurably decreasing delays that typically impede the efficiency of clinical translational research, across all participating institutions and organizations.

Disease and condition-specific research supported by NIH Institutes and Centers should be demonstrably enhanced by employing the expertise, resources, and services available at the CTSA Program Hubs, which themselves should be disease-agnostic and structured to provide innovation and support for all scientific/medical communities engaged in clinical and translational research.

Technical Assistance Video

NCATS will record a technical assistance video to review the purpose and objectives of the FOA.

The video will be available two weeks after the release of this FOA on the NCATS CTSA Funding Information page https://ncats.nih.gov/ctsa/funding.

Frequently Asked Questions

Questions may be submitted to [email protected].

NCATS will post answers to frequently asked questions on the NCATS CTSA Funding Information page at https://ncats.nih.gov/ctsa/funding.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

It is expected that the UL1 Award PD(s)/PI(s) will be an established clinician/scientist, who reports directly to an official with broad trans-institutional authority, and who personally has the authority and influence necessary to successfully promote translational and clinical research locally, partnering with internal and external stakeholders, supporting CTSA network activities as described below, and fully integrating the hub into the CTSA network nationally. This may include authority, perhaps shared with other high level institutional officials, over requisite space, protected time, promotions, institutional review boards, contracting, budgeting for clinical research, and staff qualification and certification. In loosely coupled organizations that consist of university and hospital units, the CTSA PDs/PIs should have the authority or influence, personally or on their leadership team, to integrate these independent parts of the organization toward CTSA goals. If the PD/PI oversees the institution's business office, a plan on how potential conflicts of interest will be managed should be developed. The CTSA PDs/PIs are each expected to commit at least two months and preferably three to six months effort to the award. Those with designated responsibility for defined programmatic areas of the CTSA Program should, in general, possess the knowledge, leadership, and administrative skills and capabilities necessary to direct those programs and to speak for the CTSA institution in national forums

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Additional Information on Eligibility for the Institutional Career Development Core (KL2)

Scholar Candidates

Scholars supported under the KL2 component must have a research or health-professional doctoral degree or its equivalent.

Scholar appointments

Candidates must have a full-time appointment at the application institution or a partnering institution. Support is provided for a minimum of two years and a maximum of five years of consecutive funding for each scholar, consisting of 12-month appointments.

Selection restrictions

At the time of their appointments, scholars must not have pending an application for any other PHS mentored career development award (e.g. K07, K08, K22, K23) that duplicates any of the provisions of the K component. Former or current PDs/PIs on any NIH research project grant [this does not include NIH small grants (R03), exploratory Developmental (R21) or SBIR, STTR (R43, R44 grants)] or equivalent non-PHS peer reviewed grants that are over $100,000 direct costs per year, or project leaders on sub-projects of program project (P01) or center grants (P50) are NOT eligible to participate as scholars. Appointed scholars are encouraged to apply for individual mentored K awards (e.g. K07, K08, K22, K23) and independent awards (R01, R03, R21); if successful, scholars may be required to reduce effort on the mentored career award to a minimum of six-person months and hold concurrent support from their mentored career award and a competing PHS research grant on which they are the PD/PI or component lead or terminate the KL2 appointment depending on program requirements (See NOT-OD-08-065). Scholars to be supported by the institutional career development program must be at the career level for which the planned program is intended. In keeping with the type of mentoring and career development being provided by the CTSA, a KL2 scholar candidate who is already in the process of applying for an independent mentored career development grant, a P01 grant, or R01 grant is likely too senior for the KL2 award.

Additional Information on Eligibility for the Training Core (TL1)

Trainee Candidates

Trainees supported under the TL1 component may be pre-doctoral or post-doctoral candidates seeking a research or health professional doctoral degree or its equivalent. All trainees are required to pursue their research training full time, normally defined as 40 hours per week, or as specified by the sponsoring institution in accordance with its own policies. Details on citizenship requirements and the full description of the eligible degree options are available at NRSA Policy Statement for Institutional T32 Awards.

Pre-doctoral Trainees

Pre-doctoral trainees must have received a baccalaureate degree by the beginning date of their NRSA trainee appointment. Individuals currently supported by other Federal funds are not eligible for trainee support from the T32 component.

Post-doctoral Appointments

Postdoctoral trainees must have received, as of the beginning date of the NRSA appointment, a PhD, MD, DDS, or comparable doctoral degree from an accredited domestic or foreign institution. Eligible doctoral degrees include, but are not limited to the following: DMD, DC, DO, DVM, OD, DPM, ScD, EngD, AuD, DPT, DPH, DNSc, PharmD, ND (Doctor of Naturopathy), DSW, PsyD as well as a doctoral degree in nursing research or practice. Documentation by an authorized official of the degree- granting institution certifying all degree requirements have been met prior to the beginning date of the training appointment is acceptable.

Trainee Appointments

Appointments are normally made in 12-month increments, and no trainee may be appointed for less than 9 months during the initial period of appointment, except with prior approval of the NIH awarding unit, or when trainees are appointed to approved, short-term (2-3 months) training positions.

No individual trainee may receive more than five years of aggregate NRSA support at the pre-doctoral level or 3 years of support at the post-doctoral level, including any combination of support from institutional training and individual fellowship awards

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Carol Lambert, Ph.D.
Telephone: 301-435-0814
Fax: 301-480-4660
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for A. Administrative Core)	12 pages
CTR Core (use for B. Informatics)	6 pages
CTR Core (use for C. Community and Collaboration)	6 pages
CTR Core (use for D. Translational Endeavors)	6 pages
CTR Core (use for E. Research Methods)	6 pages
CTR Core (use for F. Hub Research Capacity)	6 pages
CTR Core (use for G. Network Capacity)	6 pages
CTR Core (use for H. Optional Functions)	6 pages
Inst Career Dev (use for I. Institutional Career Development Core)	25 pages
NRSA Training (use for J. NRSA Training Core)	25 pages

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

Overall: required

A. Administrative Core: required; maximum of 1

B. Informatics: required; maximum of 1

C: Community and Collaboration: required; maximum of 1

D. Translational Endeavors: required; maximum of 1

E. Research Methods: required; maximum of 1

F. Hub Research Capacity: required; maximum of 1

G. Network Capacity: required; maximum of 1

H. Optional Functions: optional; maximum of 2

I. Institutional Career Development Core: required; maximum of 1

J. NRSA Training Core: optional; maximum of 1

When preparing your application in ASSIST, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the specific aims for the CTSA Program Hub as a catalyst for high-quality clinical and translational research, locally and nationally.

Research Strategy: This section describes the overall vision, the track record in clinical and translational research, the integration of healthcare and research and the development of a diverse research workforce.

Vision and Strategic Goals

The applicants should summarize their overall strategic goals and vision for workforce development to ensure that translational investigators and their teams have the skills and knowledge necessary to advance the translation of discoveries. Applicants should ensure high research quality through training of translational staff at all levels in appropriate, rigorous research methodology and implementation, ethics and for all those involved with human subjects research this includes training in good clinical practice as a minimum standard.

The applicants should describe their overall vision for creating a translational research environment within their own CTSA Program Hub, and within the CTSA network. Applicants should describe areas their hub will focus on and/or any unique strength or opportunity. Strategic goals under such a vision may include increased incentives for teamwork, facilitation of the assembly of multi-disciplinary translational teams, promotion of collaborative efforts, and increased knowledge and awareness of what works best in team science.

Coordination with any local partner institutions and with other CTSA Program Hubs is important to improve translational research, and to develop, to demonstrate, and to disseminate new research tools or methods. Applicants should describe the opportunities and challenges in improving clinical and translational research and training, along with innovative solutions.

The applicants should describe their vision for engagement of local and national communities in all phases of translational research, as well as increased collaboration with interdependent stakeholders (patients, clinicians, healthcare delivery systems, categorical NIH Institutes and Centers, other federal agencies, and industry).

The applicants should summarize their vision for incorporation, where possible, of translational research across the lifespan, with particular focus on pediatric and geriatric research. Further, the applicants should describe their vision of integrating special populations in translational research.

The applicants should articulate their strategic goals for improving and streamlining methods, and processes aimed at quality improvement. This includes understanding and minimizing barriers, recognizing and filling gaps, enhancing the use of parallel processes, focusing on quality control and assurance, monitoring outcomes, and obtaining feedback from stakeholders. The vision should describe the CTSA Program Hub commitment to innovation in processes and methods locally, as well as in the context of a national CTSA network. The applicants should describe their interest in and commitment to participating in a network of CTSA Program Hubs to study important clinical questions funded by NIH Institutes/Centers and other sponsors, including multi-site cohort studies or trials.

Track Record in Translational and Clinical Research

Briefly describe the institution’s contributions to translational and clinical research over the past 5 years with emphasis on high impact achievements that have advanced research towards better methods and improved health. This section should address the 5 strategic goals: (1) Workforce development; (2) Collaboration/Engagement; (3) Integration; (4) Methods/Processes; and (5) Informatics. This section should discuss prior accomplishments and progress in translational research efforts

Integration of Health Care and Research

Specific focus should be placed on the coordination between the health care delivery system and the translational research enterprise to ensure synergy and early engagement, to avoid downstream obstacles, to disseminate advances in the research domain more seamlessly into clinical care settings, and to prioritize translational research problems identified in the health care delivery context. The applicant should describe the system-wide approaches on how patients receiving care at the hub will be made aware of ongoing research, and invited to participate in research opportunities. This could occur under the concept of a learning healthcare system , designed to generate and apply the best evidence for the collaborative healthcare choices of each patient and provider; to drive the process of discovery as a natural outgrowth of patience care; and to ensure innovation, quality, safety, and value in health care.

This section should also explain how clinicians at health care facilities and in the community, are integrated in the research enterprise as active partners, including their history of referring individuals to participate in research, their plans to engage them in research, and plans to partner with them in the conduct of research and promotion of research findings. The CTSA Program Hubs are encouraged to coordinate and collaborate with other CTSA Program Hubs, and to adopt and utilize improved tools developed by others.

This section may also describe a research-friendly environment where patients seeking clinical care at the CTSA Program Hub could be routinely offered opportunities to contribute to translational research (e.g., opt-out or opt-in). Other approaches might include finding innovative ways to provide general information and education on clinical research to patients who use a CTSA Program Hub and/or partner institutions for clinical care.

Workforce Diversity

Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission.

Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the researchers, advancing the likelihood that underserved, or health disparity populations participate in, and benefit from health research, and enhancing public trust.

In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all.

This program encourages institutions to diversify their student and faculty populations and thus to enhance the participation of individuals currently underrepresented in the biomedical, clinical, behavioral and social sciences research enterprise, as described in NOT-OD-15-053. Since the program does not support high school or undergraduate participants, the disadvantaged background category (C1 and C2) is not applicable. See www.nsf.gov/statistics/wmpd.

To promote diversity within the NIH-funded scientific workforce, applicants must describe their plans to recruit a diverse workforce in their translational research program. Applicants should describe the current demographic distribution of their translational research workforce.

Applicants must describe how they will identify and address barriers that may impede the participation of underrepresented racial and ethnic minorities, persons with disabilities and women in the program. Applications should address barriers for all these underrepresented groups, and how they will be addressed.

Letters of Support: Letters of Support should state the institutional support for being part of the CTSA network. The CTSA Program is moving towards streamlined network infrastructure. State how the applicant institution and any partner institutions anticipate participation in NIH programs with full reliance on a single IRB, the use of pre-negotiated master subcontracts, and providing transparent fee for service cost listings for research items associated with NIH multi-site clinical trials.

The application must include a letter of support from an authorized institutional official stating that the institution is willing to work under a central IRB, is willing to use master subcontract agreements/trial agreements (see for example NEURONEXT Master Clinical Trial Agreement) and is willing to work under a transparent cost structure for per patient cost.

These letters should commit the institutions to the CTSA Program's goals and should indicate their willingness to work with a central IRB.

There is no cost sharing requirement under this FOA. Indication of institutional commitment to the success of the program will be considered positively in the programmatic evaluation of applications. Examples for such support may include ensuring adequate facilities or providing additional support to ensure successful collaborations.

The application is also expected to include letters from the officials responsible for intellectual property issues at the applicant institutions (including sub-contractor institutions) stating that the institution supports and agrees to abide by any Resources and Data Sharing Plan and the Software Sharing Plan submitted in the application. These letters should be clear expressions of commitment consistent with achieving the goals of the program.

General letters of support should be limited to 30.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

A Resource Sharing Plan for the CTR Cores should be described under the Administrative Core.

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study
All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project. Title this component "A: Administrative Core
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

CTSA applications submitted to this FOA shall consist of a single applicant institution, plus the possibility of one or more participating partner institutions that are effectively integrated into the proposed activities. The maximum total amount that can be requested per year for the U and K awards is 2.5% of the total institutional NIH direct cost (DC) funding for the year prior to the application and is listed at https://ncats.nih.gov/files/nih-prior-FY-award-data.xlsx.

Applicants should summarize in the first paragraph of the budget justification how they determined the maximum amount they could request by providing: 1) the name of the applicant institution; 2) the name of partner institution(s), if any; 3) the NIH DC funding amounts for each of these institutions from the currently provided NIH Funding table; 4) the total NIH DC funding amounts for applicant and partner institutions; and 5) multiply by 2.5%. If the result is less than $3 million in direct costs, you may request $3 million in direct costs; requests for more than $7.5 million in direct costs are not allowed. In addition, existing CTSA units should note the three and four-year phase-in plans described in the following paragraph. As a general principle, the amount requested should be well justified and depend on the work proposed.

If the applicant institution is currently funded by the CTSA Program at a higher level (i.e., >30% total cost of the current FY U and K awards excluding supplement and carryover actions), then the amount requested may be phased in over 3 years if needed to meet the award budget expectations described in this FOA by the beginning of year 4. It is expected that at least 25% of the reduction is proposed for year 1 funding, 50% for year 2, and 75% for year 3. For applicants currently receiving over $20M total cost in CTSA Program Hub funding, the amount requested may be phased in over 4 years if needed to meet the budget expectations described in this FOA by the beginning of year 5. It is expected that at least 20% of the reduction will occur in year 1, 40% in year 2, 60% in year 3 and 80% in year 4. A well justified plan that takes into account any changes in partners will be considered when NCATS funds the awards.

The administrative core budget should cover travel expenses for appropriate personnel (up to five people) to attend an annual in-person CTSA investigator meeting. If additional staff are identified to attend, additional justification is required as part of the Budget Justification. The expectation is that administrative operations be streamlined so that the direct cost for administration does not exceed 10% of the total UL1 direct costs. (The UL1 includes the following components: Overall, Admin Core, CTR Cores B-H.) Staff salaries and travel for the optional NRSA Training Core may be included here.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the specific aims to address organization, governance, collaboration, communication, as well as evaluation and continuous improvement and quality and efficiency.

Research Strategy:

Organization, Governance, Collaboration and Communication

Describe the organizational and governance structure and provide an organization chart. This section should describe the proposed relationship of the applicant institution and any participating partner institutions if applicable, including: what each partner will contribute; how each partner will have input and participate in decision making; and how the partners will maintain ongoing communication. It is critical that the inclusion of any partners be well justified, that they each contribute essential elements or unique strengths to the overall program, and that there is a strong plan on how the partners work closely and directly together.

Applicants should also describe the leadership succession plan for critical positions in the governance structure.

Applicants should describe how their CTSA Program Hub will engage with CTSA network activities including but not limited to 1-2 annual in person PD/PI meetings, monthly PD/PI calls, and participation in the 5 CTSA Domain Task Forces (DTF). NCATS expects that at least one PD/PI from each hub will regularly participate in these meetings, and representatives on the DTFs should be willing to be responsible for bi-directional communication. Applicants should indicate their willingness to serve on the Steering Committee, consisting of CTSA PDs/PIs, NIH staff, FDA representation and a public member. NCATS expects that Steering Committee members regularly participate in monthly PD/PI calls, communicate via email in the interim, and participate in 3 annual in person Steering Committee meetings. Applicants should describe a detailed plan on how they will maintain bi-directional flow of communication between their CTSA Program Hub research community and the Steering Committee. Applicants should also describe their willingness to participate in telephone and email communications between the Steering Committee members and the hub PDs/PIs they each represent.

Applicants should describe plans for managing competing institutional perspectives, disparities in institutional culture and resources, and sharing of institutional expertise and resources. Plans for collaborative leadership and communication should consider the inclusion of a diverse range of internal and external partners and stakeholders. If an applicant institution is working with PCORnet, applicants should develop strong, synergistic activities with PCORnet Projects and provide an explicit plan to foster collaboration. In addition, NCATS is encouraging applicants to invite one or several PCORnet leaders to their CTSA organizational group. To promote synergy between the UL1 Award lead, the K Award lead, and if applicable, the T Award lead, a collaborative leadership and communication plan between research, career development, and training should be described that integrates the educational programs of degree-granting institutions in clinical and translational science with the other partners at the CTSA Program Hub.

Evaluation and Continuous Improvement

NCATS is working with the CTSA Program Steering Committee and the investigator community to develop a set of common metrics across the CTSA Program Hubs. Applicants should describe their capacity to collect data to evaluate the impact of their CTSA Program Hub.

Applicants should also describe how they will consult their External Advisory Committee (EAC), a group that each CTSA Program Hub must have. This EAC should meet annually to review progress and offer recommendations to the CTSA PD(s)/PI(s). Applicants with an existing EAC should name the members of their EAC and should describe changes they have made in response to EAC recommendations.

Applicants without an existing EAC should describe their plans for constituting an EAC; the types of expertise to be represented in the EAC should be broad and include stakeholders that can bring a range of important perspectives such as patients, community-based clinicians, health systems representatives, experts in informatics, and industry. Applicants should describe their plan for EAC membership accordingly, but should not specify names and should not contact potential EAC members in advance of review of the application. In this section, applicants must also describe how the internal leadership and the external advisory board will be presented with metrics and related information so that they can take corrective action as needed, or identify particularly winning strategies for further dissemination.

Whenever possible, applicants should consider an experimental approach to evaluating innovations in training or research implementation. Different units of one CTSA Program Hub, or several collaborating CTSAs could, for example, be randomized to the innovative intervention in training or research, and then prospectively compared to those randomized to standard practice. This will allow for subsequent data-driven decisions.

Quality and Efficiency

This section should describe the CTSA Program Hub s overall commitment to quality, and plans to ensure safe and ethical human subject research, including the appropriateness of study design, feasibility, recruitment, timely closure of futile studies, research study workflow, analysis, and dissemination of results. Applicants should also describe how they will provide high quality study drug management.

Applicants should describe how quality will be planned, monitored, and how interventions will be implemented when needed. Applicants should also describe how they will foster innovative methods and operational principles; how they will demonstrate the effectiveness of the innovation; and if useful, how they plan to disseminate their findings.

Applicants should also describe a system-wide approach to increase efficiency that includes plans for parallel processing, monitoring research timelines, review processes to identify opportunities for increased efficiency, and systematic approaches to streamlining administrative processes through innovation.

Letters of Support: Only letters of support specific to the Administrative Core should be attached to this section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

The CTSA Program encourages sharing of resources with broad availability of policies, practices, materials, and tools to facilitate collaboration, reuse, and replication. In addition, the CTSA Program encourages sharing of research data in a timely manner with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Thus, the CTSA Program expects awardees to implement a Resource and Data Sharing Plan consistent with achieving these program goals.

The CTSA Program encourages sharing of software and code that are developed or modified to accomplish aims of this program. This may include, but is not limited to, software, tools, or code sets for: extraction and use of data for research from clinical systems; implementation of new efficient workflows for research studies; innovative networking to connect scientists, patient communities, industry, resources, data, and ideas; novel analytic and analysis programs; and educational tools. While software development is not the primary goal of this program, it is expected that software or sets of code may be developed under this program. Thus, awardees and their sub-contractors are expected to implement a Software Sharing Plan consistent with achieving the goals of this program.

A Resource and Data Sharing Plan is expected to be included in the application, and should include a plan for the sharing of software. There is no particular software dissemination license required for this program. However, NIH does have goals for software sharing and reviewers will be instructed to evaluate the sharing plan relative to the following goals:

• The software should be freely available to biomedical researchers, health care systems, and research institutions or organizations.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages.
• The terms of software availability should include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with other colleagues.

This section should encompass the Resource Sharing Plan for all the CTR Cores.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

Informatics is a high priority, overarching function that can transform translation at the CTSA Program Hubs and in the CTSA network. Informatics resources, support, expertise, training, collaboration and innovation are critical to a successful translational research environment.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Informatics)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project- Title this component B. Informatics .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Informatics)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Informatics)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Informatics)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Informatics)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Informatics)

Budget forms appropriate for the specific component will be included in the application package.

Because of its broad scope and overarching importance, there is no recommended limit to scope and budget (as done for the specific functions below). Applicants should plan for robust informatics resources and strong personnel and leadership within a budget range adequate to the scope and critical importance of informatics which will likely exceed the range indicated for specific unctions below.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Informatics)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Informatics component.

Specific Aims: Describe specific aims for this high priority overarching CTSA function.

Research Strategy: Biomedical informatics is a critical CTSA focus for enabling and advancing translational research, which is increasingly data intensive, and requires collaboration across many communities, including healthcare, research, and public health. Additionally, the increasing amounts and types of data (e.g., genetic, imaging, clinical, economic, environmental, behavioral, patient reported) need to be integrated to generate knowledge. Applicants should propose a synergistic plan to use informatics across the entire spectrum of translational research activities at the hub, in support of pre-clinical and clinical research, as well as community engagement, user training, and education. Approaches are highly encouraged that integrate data from different sources such as clinical databases, research datasets, sensors, mobile technology, social media, patient generated data and publicly available data sources.

CTSA Program Hubs should offer researchers a user-friendly data management system along with training on its use and some basic support. CTSA applicants should encourage compatibility of their research systems with broadly accepted content and technical standards including those adopted by the Department of Health and Human Services for use in U.S. health care and public health operations. In addition, as NIH Institutes and Centers adopt common data elements in their domain areas, CTSA Program Hubs should ensure their research tools are compatible (see http://www.nlm.nih.gov/cde/) for more information).

Maintaining the security of study data, particularly in studies involving human subjects, is critical. Some clinical and translational researchers manage such data in systems, processes, and formats that lack appropriate security. Academic institutions should provide low cost and user-friendly infrastructure to assist investigators in ensuring the security of their data, and clear requirements for its use by faculty, staff, and students.

Applicants must describe their plan for ensuring the security of research data on all studies involving human subjects at all participating institutions. This plan should address policy, workflow, technical, and enforcement issues. The plan should outline challenges and possible alternative approaches for surmounting them.

CTSA Program Hubs should work towards a flexible, sustainable digital enterprise where digital assets are interoperable so that, for example, data from the electronic health record (EHR) can be used for research purposes. This will require informatics solutions that are embedded in HIPAA regulations and other measures to safeguard patient privacy and autonomy. Cooperation and coordination among the data stewards in various organizations and institutions on policy issues, and among the managers of those data systems on technical issues are critical. This section should include a description of the efforts towards interoperability of various informatics platforms, data harmonization, facilitation of data exchange among diverse sources, and the interface of electronic medical records with research data systems.

CTSA Program Hubs should support a research-friendly integrated IT environment where information on applicable research opportunities is presented to clinicians and patients via EHR at the time of the clinical encounter. Other useful services might include noting a patient’s participation in a research study in the clinical EHR for the benefit of the treating clinician, and efficient routing of laboratory results. Applicants should describe any solutions they already have locally to integrate health care and research data, as well as plans for the future. Applicants should indicate if they are currently participating in initiatives that make use of EHR data for research or surveillance (such as for example Mini-Sentinel, PopMedNet/PCORNet, i2b2, or SHRINE), and how they integrate participation with these initiatives into their local digital enterprise and network activities.

Applicants should describe how they will establish and maintain a sustainable research data warehouse, and how they will build, grow, train, and maintain a research data warehouse team. Applicants should explain their ability to query the EHR across the multiple units of their institution, and its partners, including for example outpatient clinics. Applicants should indicate their current capacity to provide analyses in response to queries, and any plans to increase capacity when needed. Applicants should also define their approach for ensuring data quality (fit for purpose), and indicate how they will institute a quality management plan. Applicants should enumerate standard terminologies they are using, and how they will incorporate new standards. Applicants should also describe how they will develop and share new standards in cases where there are no existing standards. Applicants should indicate how they will contribute to best practices in research data warehousing across the CTSA network and in collaboration with other initiatives such as PCORNet. Applicants should describe their ability to respond to diverse types of queries, including the number of potential participants meeting study entry criteria with regards to age, primary and secondary diagnoses (ICD), current medications, etc.

To accelerate translation, CTSA Program Hubs should work towards data sharing and enabling data access, integration and processing. Applicants should also describe how they might collaborate with other CTSA Program Hubs on using common data standards in multi-site projects. Applicants should indicate whether they have initiatives at their hub that support data sharing, how they promote broad use of data, and how they encourage investigators to submit data to repositories (see for example NIH Data Sharing Repositories). In this context, applications should also describe how they train researchers to prepare for downstream data sharing, such as by providing training and sample language for research-friendly consent forms that support broad data use (not limited to time, place or purpose), and that avoid complex nested formats to the extent possible. This is based on the observation that patients consenting to research participation are often information altruists who welcome the secondary use of research data so long as appropriate measures have been taken to protect their privacy.

The informatics leadership from each CTSA is expected to participate in national CTSA network informatics activities. The application should indicate an informatics point person that can serve as liaison to the network. The CTSA Program Hubs are encouraged to share their informatics tools, and to adopt and utilize tools developed by others to avoid duplication and redundancy. The CTSA Program Hub must be committed to working toward adoption and implementation of standards and practices endorsed by the CTSA Program.

Letters of Support: Only letters of support specific to Informatics should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Community and Collaboration)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component C: Community and Collaboration .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Community and Collaboration)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Community and Collaboration)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Community and Collaboration)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Community and Collaboration)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Community and Collaboration)

Budget forms appropriate for the specific component will be included in the application package.

The overarching, high priority functions addressed here are highly important for creating the right environment for successful translational research. They do not have a recommended limit to scope and budget (as done for the specific functions below) because they are critical across almost the entire spectrum of translational activities. Applicants should budget for robust resources and adequate personnel and leadership for each of these critical functions; community engagement, collaboration and multi-disciplinary team science. The budget range for each area should be adequate to the scope and critical importance of these overarching functions and will likely exceed the range indicated for specific functions below.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Community and Collaboration)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Community and Collaboration component.

Specific Aims: Describe specific aims for this high priority overarching CTSA function.

Research Strategy:

Community Engagement

This section should describe how the CTSA Program Hub will engage communities, defined broadly, in the translational research enterprise. In this context, the term community includes all stakeholders connected to clinical and translational research. Communities may include but are not limited to non-profit or industry entities engaged in translational research, and might include disease advocacy groups, local health providers, community-based organizations, and other national or local communities.

The benefits of engaging patients and communities not only as consumers of healthcare, but as active partners in the full spectrum of translational research include, but are not limited to: identifying community health needs and priorities, providing input on relevant research questions, contributing to appropriate research design and methods, developing culturally sensitive and ethical proposals, enhancing the recruitment and retention of research participants, and implementing and disseminating research findings more effectively. Most community engaged research has taken place in the later phases of translational research, so that there is less experience on how to identify and involve communities from the early research stages and throughout the translational continuum. In addition, since the optimal ways to involve relevant communities in each stage of the translational process have not been defined, there is a need for community engagement to be addressed as a scientific problem, in order to identify best practices and most effective approaches in an experimental, data-driven fashion.

Applicants should describe how Community Engagement will be integrated into the translational science spectrum, and specifically how community engagement will be integrated into leadership, integration, research, and communication strategies at their hub. CTSA Program Hubs may engage communities based on a geographically defined area, a defined population or a disease entity. Communities to be engaged may be physical or virtual online communities.

Each institution is encouraged to build on their existing capacity and expertise in community engaged research and to evaluate which approaches or programs most contribute to advancing the process of turning observations in the laboratory and clinic into interventions that improve the health of individuals and the public. The guiding principle should not be to create community engagement infrastructure for the sake of it being there, but to engage communities around specific projects and to advance the science of community engaged research. Applicants should therefore describe how they will use the CTSA resources provided to develop best practices, information materials, and consultations on how to engage communities around specific projects. Applicants may also describe in this section how they will acknowledge community engaged research in academic policies (such as promotion and tenure), how they will develop culturally competent training, how they will provide training for staff and communities (e.g. training for patients participating in clinical and translational research), how they will foster innovation, and how they will participate in the dissemination of best practices. The CTSA Program Hubs are encouraged to coordinate and collaborate with other CTSA Program Hubs, and to adopt and utilize tools developed by others to avoid duplication and redundancy.

If successful, community engagement would help ensure that communities have the capacity to participate as full partners; that communities are consulted for their research priorities; that all stakeholders are respected, valued and rewarded for their time and expertise, that more effective implementation and dissemination strategies are developed, and that there is increased public support for research, and ultimately improvements in the health and well-being of communities.

Collaboration and Multi-Disciplinary Team Science

Applicants should describe how they will foster collaborations by providing education in team science to promote the development and implementation of multi-disciplinary teams, including the inclusion of racial or ethnic minorities or persons with disabilities and how complexities like the presence of racial and ethnic minorities impact the function of multi-disciplinary team science, and best practices. Applicants should plan for ways to identify best practices in team science, and to disseminate successful models. This should include consideration on how team scientists will be evaluated in the academic promotion context, as well as consideration of enhancing the professional experience for all members of a multi-disciplinary translational team, not only the lead researcher. Applicants may describe for example how practicing clinicians, pharmacologists or statisticians, often critical to success in translation, will be professionally recognized and thus incentivized to engage in collaborations. This may also include using innovative measures (other than the sole use of publications or grant support) when evaluating researchers. These measures could focus for example on contributions to therapeutics development (such as patents, or the impact of research advances). Further, applicants should describe how they envision working with other CTSA Program Hubs and the national network, for example through shared online courses or best practices. Applicants may describe innovative models on how to promote collaborations, such as conferences for multi-disciplinary researchers centered on a specific disease, agreements that facilitate collaboration/team science, or work on a translational roadblock or unmet need to spark collaborations and innovative solutions. Another approach is to offer consultations to investigators by a multi-disciplinary team of experienced translational experts so that researchers can better understand next steps, timelines, and plan to assemble the appropriate team of collaborators.

Letters of Support: Only letters of support specific to Community and Collaboration should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Translational Endeavors)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component D: Translational Endeavors .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Translational Endeavors)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Translational Endeavors)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Translational Endeavors)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Translational Endeavors)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Translational Endeavors)

Budget forms appropriate for the specific component will be included in the application package.

The budget will depend on the development needs for each hub to reach the strategic goals. For the specific, required functions below, tasks are defined, and associated with budget suggestions adjusted for the anticipated award size to clarify expectations of scope. The tasks are listed below showing in parentheses the recommended direct annual costs budget amount in $1000s for small (total anticipated CTSA award <$4.5M DC), medium (total anticipated CTSA award $4.5M-$6M DC), and large awards (total anticipated CTSA award >$6M-$7.5M). The amount requested should be well justified and depend on the work proposed.

1. Translational Workforce Development (TWD) (200, 300, 400)

Applicants should budget for workforce development for hubs with small, medium and large awards (defined above). Education administration or project management expenses and support for the TWD-liaison to network-wide activities may be included. Further, the budget needed may be used for continuing education in translational research related for health care professionals who are associated with hubs; and development of innovative, online tools or training collaborations in continuing education in translational research with other CTSA Program Hubs, the CTSA network, and other entities.

2. Pilot Translational and Clinical Studies (PTC) (200, 300, 400)

Most of the PTC funding should be allocated to pilot projects, with a small amount for review and administration of the program. The PTC must not support any clinical trials beyond phase IIA. NCATS can develop and provide infrastructure and resources for all phases of clinical trials, but it can directly support clinical trials only through the end of phase IIA.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Translational Endeavors)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Translational Endeavors component.

Specific Aims: Describe the specific aims for how the clinical and translational workforce will be trained in clinical research methodology and how pilot study program will be addressed.

Research Strategy:

Translational Workforce Development (TWD)

For this function, applicants should describe a comprehensive approach to the continuous development of a diverse translational workforce at the CTSA Program Hub. This needs to be well integrated with the Career Development and Training components of the overall U54 program, the CTSA Program Hub. The workforce development should be directed not only at physician scientists, but also at members of translational and clinical research teams, such as pre-clinical translational scientists, research coordinators, and other allied health professionals involved in human subject research. Applicants should describe their plans for implementing continuing education in Good Clinical Practice (GCP) of personnel engaged in NIH defined clinical trials. The training opportunities offered should include competencies that are important to translational research such as regulatory sciences, or entrepreneurship. The continuing education programs should be adapted to insure, to the extent possible, high level performance by all members of the research team. The continuing education programs may include on-site and on-line opportunities, and should be tailored, practical and interactive. They may be designed around relevant, real-world scenarios to be solved individually or by teams. The training experience should emphasize that translational and clinical research is a collaborative endeavor.

Applicants should describe how existing training programs will be offered to the CTSA staff or adapted to their specific needs, and how they will streamline resources and avoid redundancy by collaborating with other CTSA Program Hubs or related training efforts. To that effect, applicants should appoint a liaison to interact with the emerging network-wide training and staff qualification initiatives.

Pilot Translational and Clinical Studies Program (PTC)

Each CTSA Program Hub has the flexibility to focus and design their translational pilot program to address their particular priorities; however, the program should not exclusively focus on a select disease category, a few diseases or specialties, or on a limited number of investigators. In keeping with the NCATS mission to catalyze translation of discoveries to treatments, the pilot studies funded under the CTSA Program should focus on translational and clinical research rather than on basic discovery research. A preferred, but not required, characteristic would be if such research did not only address a translational research question, but also provided insights that could be generalizable to other projects. Such research would advance translational science, the discipline focused on understanding and addressing the scientific and organizational challenges underlying each stage of the translational process. Applicants should not include detailed and specific pilot projects to be reviewed as part of their U54 application.

Applicants should describe their translational pilot program guidelines, addressing: solicitation, review, prioritization, business and cost management, progress tracking, and program evaluation. The review must be rigorous and include a meeting of a multi-disciplinary committee patterned after an NIH study section during which pilot project reviewers interact as a group in real time to discuss the applications. The process will help to ensure pilot projects are of high methodological quality, and can answer important scientific questions proposed. Two-level reviews are allowed; a larger group of reviewers with specialized expertise may submit written critiques that are then considered by a smaller multidisciplinary group interacting in real time to make the final decision Pilot studies should have a clear path forward along with criteria for go/no go decisions, next steps if the pilot is successful, and plan for reporting of negative results if not successful. Applicants also should discuss their experience or interest in adopting any emerging CTSA review standards, or participating in reciprocal review support to exchange expertise. The CTSA Program Hubs are encouraged to coordinate and collaborate with other CTSA Program Hubs, and to adopt and utilize tools developed by others to avoid duplication and redundancy. Appropriate policies must be included to ensure translational pilot project compliance with all federal regulations and NIH policies, including, but not limited to, studies involving human subjects, genetic material, stem cells, or model organisms.

Metrics: For all specific functions described above, NCATS in collaboration with the CTSA Steering Committee is developing common metrics to measure the impact of the CTSA Program and will work on implementation with successful applicants. For each function discussed, applicants should describe their capacity to collect common metrics and may propose metrics they favor for each of the required functions.

Letters of Support: Only letters of support specific to Translational Endeavors should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Methods)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component E. Research Methods .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Methods)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Methods)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Methods)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Methods)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the
• component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Methods)

Budget forms appropriate for the specific component will be included in the application package.

The budget will depend on the development needs for each hub to reach the strategic goals. For the specific, required functions below, tasks are defined, and associated with budget suggestions adjusted for the anticipated award size to clarify expectations of scope. The tasks are listed below showing in parentheses the recommended direct annual costs budget amount in $1000s for small (total anticipated CTSA DC award <$4.5M DC), medium (total anticipated CTSA award $4.5M-$6M DC), and large awards (total anticipated CTSA award >$6-$7.5M DC). The amount requested should be well justified and depend on the work proposed.

1. Biostatistics, Epidemiology and Research Design (BERD) (200, 300, 400)

Appropriate budget items would include for example the support of expert time for consultations, for project management time to coordinate course and training opportunities, and to connect methodology researchers with others who have identified a gap in translation that could be filled through methodological innovation.

2. Regulatory Knowledge and Support (RKS) (150, 300, 400)

Appropriate budget items would include for example the support of regulatory experts and protocol writers to provide consultations and assistance to investigators who submit IND applications, or in other regulatory matters including innovative strategies such as remote monitoring or risk-based monitoring. Other appropriate expenditures might include provision of information and access to coursework in regulatory sciences.

It is evident that not all research conducted at an academic medical center could receive support from finite CTSA resources. Because the mission of NCATS and the CTSA Program is disease-agnostic, CTSA funds can therefore not be used to offset the cost for a necessarily select set of disease-oriented research studies. As a general principle, therefore, the CTSA funding should be used to facilitate and catalyze research supported by other funders (with the exception of those pilot and collaborative studies that are funded by the CTSA Program itself). An important operational principle of all NCATS programs, including the CTSAs, is to maximize impact via a catalytic approach: developing, demonstrating utility of, and then disseminating improvements in translational science and operations. The CTSA support should thus focus on providing a foundation that promotes quality, efficiency, collaboration, and ultimately success as defined by impact. This support should also be used to identify roadblocks and to foster innovation to overcome them. Administrative costs should be carefully considered and justified. Examples of appropriate funding requests may include a limited number of experienced research professionals who can provide oversight, consultations, education, serve as liaison between different partners, help with quality control and assurance, and promote innovation, but who cannot provide the actual research procedures (except those included under the voucher program described in detail below and accounted for separately).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Methods)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Research Methods component.

Specific Aims: Describe the specific aims to lay the foundation for high quality research and how high-quality biostatistics and regulatory support will be provided.

Research Strategy: For each of the required functions below, applicants should describe how CTSA funding will be used to enhance innovation, access, and quality in a measurable way.

Biostatistics, Epidemiology and Research Design (BERD)

The BERD function must include service and continuing education elements to provide to investigators support for clinical research design and analyses, and provide educational topics and courses for research staff. BERD also should include an academic research section capable of developing novel tools and methods intended to solve problems and address barriers that impede the conduct of clinical and translational research projects.

BERD will include user-friendly continuing education courses for research staff at all levels, which are integrated with and stimulated by the work environment so that everyone in the research enterprise is continually exposed to these foundational methods. BERD cannot provide the entire range of possible coursework, but can facilitate access, raise awareness of learning opportunities, and collaborate with entities such as the department of biostatistics, or with other CTSA Program Hubs or external groups. BERD may also help develop a degree or certificate in clinical and translational biostatistics open to trainees with a range of primary degrees. Applicants should describe their plans to include innovative approaches such as online continuing education classes or interactive programs.

BERD will develop and promote innovations in tools and methods intended to address barriers to translational and clinical research. This will be done in collaboration with internal groups, groups at other CTSAs or external groups. BERD cannot support all innovations itself, but helps to identify the gap and opportunity, and to connect the collaborators needed to solve the problem.

BERD will provide easily-accessible consultations in biostatistics, epidemiology, research design, and analysis. BERD cannot furnish comprehensive statistical support for all translational research projects. For each project, adequate methodological support must be planned for and included in any funding request to a sponsor. The BERD consultations should be limited in scope and intended to help researchers understand the underlying methodological aspects of their research so that they can adequately plan their projects. In addition, BERD consultations are intended to help connect researchers with expert collaborators for additional or ongoing support.

Applicants should describe how they might collaborate with other CTSA Program Hubs to leverage resources, or to demonstrate and disseminate BERD innovations.

Regulatory Knowledge and Support (RKS)

RKS provides regulatory knowledge and facilitates compliance related to clinical and translational research in conformance with IRB policies, State laws, and Federal regulations. Applicants are encouraged to innovate at all levels of clinical and translational research including, for example, the provision of integrated research education, guidance, services, or tools for protocol and informed consent development, adverse event reporting, safety and regulatory management, and compliance. Educational resources might be available remotely, and could be harmonized or shared with other CTSA Program Hubs or external entities. The CTSA Program Hubs are encouraged to coordinate and collaborate with other CTSA Program Hubs, and to adopt and utilize tools developed by others to find and use best practices. Regulatory support provided through the CTSA should neither take the place of an institutional compliance office nor be responsible for Institutional Review Board (IRB) activities, but should assist investigators, coordinators and others as needed. The institution should demonstrate innovation to streamline regulatory support without loss of participant protections and should promote regulatory competency, regulatory science, and new regulatory-compliant strategies for emergent technologies. Examples include improvements to the informed consent process which may include innovative approaches to limiting the total number of pages to 5-8, or to making the informed consent form more user-friendly and informative, by separating legal and contractual language from the information that is of importance to research participants, and/or by providing supplemental video or other visual material. Applicants should describe how they might collaborate with other CTSA Program Hubs to leverage resources, or to demonstrate the value of RKS innovation.

Metrics: For all specific functions described above, NCATS in collaboration with the CTSA Steering Committee is developing common metrics to measure the impact of the CTSA Program and will work on implementation with successful applicants. For each function discussed, applicants should describe their capacity to collect common metrics and may propose metrics they favor for each of the required functions.

Letters of Support: Only letters of support specific to Research Methods should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Hub Research Capacity)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component F: Hub Research Capacity .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Hub Research Capacity)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Hub Research Capacity)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Hub Research Capacity)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Hub Research Capacity)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Hub Research Capacity)

Budget forms appropriate for the specific component will be included in the application package.

The budget will depend on the development needs for each hub to reach the strategic goals. For the specific, required functions below, tasks are defined, and associated with budget suggestions adjusted for the anticipated award size to clarify expectations of scope. The tasks are listed below showing in parentheses the recommended direct annual cost budget amount in $1000s for small (total anticipated CTSA award <$4.5M DC), medium (total anticipated CTSA award $4.5-$6M DC), and large awards (total anticipated CTSA award >$6-$7.5M DC). The amount requested should be well justified and depend on the work proposed.

1. Integrating Special Populations (ISP) (200, 300, 400)

Appropriate budget items might include identifying point persons for pediatrics research, for geriatrics research, for populations affected by health disparities, for rare disease populations, or for other special populations. Such a person could identify opportunity, establish best practices for including an increased range of the study population, provide consultations, foster collaborations, and effect policy changes to enhance opportunities for ISP.

2. Participant and Clinical Interactions (PCI)* (400, 750, 1000)

CTSA funding should be used to support clinical research staff only for oversight and quality assurance, but not to support actual research activities that are part of studies and trials conducted at the CTSA Program Hub. For example, the CTSA funding may be used to support a limited number of experienced clinical research professionals such as research nurses or coordinators who can facilitate access to resources, can assist study-specific staff, and can provide oversight and help with quality control and assurance. Support for the study-specific staff conducting the actual research participant evaluations must be included in the per-patient fee or other funding provided by the NIH ICs or the private sector supporter of that study or trial. If a pool of coordinators or research nurses is available to conduct participant evaluations and implement protocols at a CTSA Program Hub, their activities must be charged to the study budget itself. For further clarification see NCATS Policy Statement in NOT-TR-17-012.

Space to conduct research cannot be charged to the CTSA award. If research space is provided by the institution for inpatient and or outpatient participant evaluations, the application should describe the space in Facilities and Other Resources, potential availability and if applicable hourly or overnight rates charged for NIH-funded or other research. Inpatient and outpatient care costs cannot be charged to the CTSA award.

The cost of evaluations such as laboratory testing or imaging should be included in the budget for each specific study and included in the funding for that study. The cost for these tests cannot be charged to the CTSA award. The only exceptions are existing commitments to complete ongoing studies (see below), and the option of including a "voucher" program. Such a voucher program can provide small amounts of support for research participant evaluations, for instance laboratory testing in investigator-initiated studies (Including those funded by the CTSA or those that are part of the NCATS K-award program). The total suggested amount for a voucher program should be less than $100,000 for small; $200,000 for medium; and $300,000 for large academic medical centers (tiers as defined above). The vouchers have to be approved by a committee with members from different departments or schools as applicable, can go to IRB approved studies only, and it is suggested that it should generally range between $ 1000 and $5000 each.

If an institution is currently funded under the CTSA Program, and if support for research participant evaluations (tests, procedures, and staff time) is currently provided through the CTSA award, the applicants may choose to describe a transition period of up to three years when needed during which funds may still be used for research participant evaluations. This is to allow for a transition to the current model, and to lessen the impact on ongoing projects. This gives applicants flexibility when budgeting for participant evaluations within the limit of the Award Budget described in Section II which remains unchanged.

* Space, beds, or study participant evaluation (e.g. laboratory testing or imaging) are not allowable costs outside of a voucher program which may be used for investigator-initiated studies that do not have sufficient dedicated funding. Through such a voucher program only, and after rigorous and standardized internal review, qualified investigator-initiated studies may receive a defined amount towards costs related to research participant evaluations.

Budget Justification: For all tasks described in the functions above, the amount requested must be well justified. The budget justification should list each function identified above and a corresponding justification for the associated costs.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Hub Research Capacity)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Hub Research Capacity component.

Specific Aims: Describe the specific aims for the integration of special populations (such as pediatric and geriatric) into research and the aims for participant and clinical interactions.

Research Strategy: For each of the required functions below, applicants should describe how CTSA funding will be used to enhance innovation, access, and quality in a measurable way.

Integrating Special Populations (ISP)

Translational Research is needed to ensure that breakthroughs are quickly translated to the benefit of society and all subpopulations within. Significant evidence gaps remain in our understanding of childhood diseases, and of the effect of treatments on children. As a result, clinicians must often take action based on data from adults. Applicants should describe efforts to include children as a focus of translational research.

With the graying of the US population, investigators must recognize and adapt to population longevity and the questions so driven. Applicants should describe efforts on how older patients will be included in research, for example how they might increase or drop the upper age limit for research participation. Another special group includes those who are the survivors of formerly lethal childhood diseases. Research is needed to better understand the impact on and approach to adults with chronic health conditions that originated in childhood, both as a consequence of the disease or its treatment.

In addition to considering longitudinal differences across the lifespan, translational research must also consider cross-sectional differences across populations, such as minority, underserved or health disparity populations, which includes racial, ethnic or gender differences as well as differences in socio-economic status or in a rural vs. urban environment. This may also include other populations such as pregnant women, people with particular disabilities, and hard-to-reach groups that are often impacted by health disparities. Applicants should describe how they might collaborate with other CTSA Program Hubs to leverage resources. Applicants are encouraged to adopt and utilize useful tools developed by others.

Participant and Clinical Interactions (PCI)

CTSA applicants must describe detailed plans to ensure that high quality human subjects research is conducted at their institutions and that scientifically or ethically flawed studies are identified, not approved or conducted, and learned from at an individual and institutional level. The application should address the appropriateness of specific study designs, development of realistic recruitment goals, tracking of enrollment, follow-up, submission of high quality data, careful data monitoring, steps to ensure the timely assessment of feasibility and closure of studies that do not meet goals or suggest toxicity or breach boundaries established to identify efficacy, and orderly closeout and publication of results. There should be efficient institutional workflows for planning and conduct of studies, the evaluation of patients by trained personnel, expectation of prompt analysis, and dissemination of results.

CTSA Program funding is at the moment fixed, but clinical and translational research opportunities are likely to continue to increase, given the rapid pace of advances in fundamental research. Funding for specific clinical and translational research projects must therefore come from a variety of sources in addition to the CTSA Program itself, such as the disease-specific NIH Institutes and Centers (ICs), or the private sector. The CTSA Program must ensure quality and efficiency so that these sources come to value the CTSA Network because of dependable and efficient processes, leading to timely completion of trials with lower overall cost as a result of more efficient implementation. For further clarification see NCATS Policy Statement in NOT-TR-17-012.

Additionally, the registration of all clinical studies and trials in clinicaltrials.gov is expected; registration of all applicable trials is required, as is the posting of results as required by Food and Drug Administration Amendments Act (FDAAA). Applicants should describe any education or support they provide to clinical investigators for registering or reporting on the clinicaltrials.gov website.

Metrics: For all specific functions described above, NCATS in collaboration with the CTSA Steering Committee is developing common metrics to measure the impact of the CTSA Program and will work on implementation with successful applicants. For each of the functions discussed, applicants should describe their capacity to collect common metrics and may propose metrics they favor for each of the required functions.

Letters of Support: Only letters of support specific to Hub Research Capacity should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Network Capacity)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component G. Network Capacity .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Network Capacity)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Network Capacity)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Network Capacity)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Network Capacity)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Network Capacity)

Budget forms appropriate for the specific component will be included in the application package.

The budget will depend on the development needs for each hub to reach the strategic goals. For the specific required functions below, tasks are defined, and associated with budget suggestions adjusted for the anticipated award size to clarify expectations of scope. The tasks are listed below displaying in parentheses the recommended direct annual cost budget amount in $1000s for small (total anticipated CTSA award <$4.5M DC), medium (total anticipated CTSA award $4.5-$6M DC), and large awards (total anticipated CTSA award >$6M-$7.5M DC). The amount requested should be well justified and depend on the work proposed.

1. Liaison to Trial Innovation Centers (LTICs) (200, 350, 400)

Based on the research volume at the hub (small, medium, or large awards), the applicant may include costs for staff with legal, IRB, budgeting, or project management expertise to work with planned Trial Innovation Center (TIC) activities. ( RFA-TR-15-002.)

2. Liaison to Recruitment Innovation Centers (LRICs) (200, 300, 400)

Based on the research volume at the hub (small, medium, or large awards), the applicant may include costs for staff with data, informatics, analysis, privacy protection, study recruitment, communications or project management expertise to work with the planned Recruitment Innovation Centers (RIC) activities. ( RFA-TR-15-004)

Budget Justification: For the functions described above, the amount requested must be well justified. The budget justification should list each function identified above and a corresponding justification for the associated costs.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Network Capacity)

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Network Capacity component.

Specific Aims: Describe the specific aims to address the support of network wide studies and aims for optional activities in areas of unique strength or opportunity.

Research Strategy: Applicants should describe how the CTSA Program Hub will connect with the CTSA network resources and how it will support multi-center studies. For each of the functions below, applicants should describe how CTSA funding will be used to enhance innovation, access and quality in a measurable way.

Liaison to Trial Innovation Centers (LTICs)

To facilitate clinical research, applicants should develop a local trial innovation unit that streamlines and facilitates study start-up and implementation. The unit might include staff experienced in IRB activities, contracting, budgeting for clinical studies, as well as coordination and project management. The local trial innovation unit will work on accelerating IRB, budgeting, contracting and other start-up timelines through parallel rather than sequential work steps, and through process re-engineering. The unit will track study metrics related to study start-up, implementation and close-out, working with a CTSA network-wide initiative that is developing common metrics for the CTSA Program. The unit will also serve as liaison to the CTSA Trial Innovation Centers (TICs), including implementing IRB reliance and pre-negotiated master subcontracts.

The subsequent task of the study unit will be to support application for IRB approval of specific

protocols and the execution of trial-specific amendments to the master subcontract agreements to be established between the CTSA Program Hubs and the TICs. Examples of IRB reliance agreements and master contracting templates used by the NIH can be found at NEURONEXT Central IRB. Applicants and authorized institutional officials are strongly encouraged to review these documents carefully, and to anticipate a comparable framework for TICs.

The objective of the TICs and the network they will create is to streamline the implementation of clinical research. While NIH has historically often funded trials to test drugs already approved for other indications, the network is intended to assure the broadest access to any new therapies for patients by carrying out trials derived from partnerships between NIH and industry, foundations, or academia. These trials will utilize a variety of the NIH agreement mechanisms (e.g., Cooperative Research and Development Agreements [CRADAs]) that facilitate industry participation and support. (See for example, NEURONEXT CRADA.) However, the streamlined infrastructure created by the TICs and the CTSA network are anticipated to not only benefit clinical trials, but also epidemiology studies or observational cohort studies contributing to precision medicine.

The applicant should describe how the unit will coordinate between reliance on a central IRB and the other research oversight tasks carried out at the institution, such as radiation safety approval, or conflict of interest reporting and management. CTSA applicants and participating institutional groups should anticipate and agree, in principle, to work collaboratively with other institutions and with funding agencies to facilitate participation by their research teams in multi-site studies. They should indicate their willingness to adopt centralized IRB arrangements. Applicants should describe institutional processes for clinical trial agreements and subcontracts and likely timelines for completion. Applicants are also encouraged to engage their authorized institutional official(s) in addressing this section of the FOA.

Specifics on interactions between the local study units and the TICs are expected to be defined in the form of joint standard operating procedures once the TICs are established. Therefore, applicants should describe in detail how they will work locally to aid efficient trial implementation, and should describe in general terms only their capacity and willingness to engage with the TICs.

Applicants should include a table with the application that contains a brief description of all NIH defined Phase III clinical trials with site activation in the first half of the calendar year prior to the application, with metrics that include time from contract received to execution, time from protocol received by the trial PD/PI (or time protocol finalized if local trial) to IRB approval, time from subcontract executed to first patient first visit, and time from IRB approval to first patient first visit. For investigator-initiated, single-site studies, site activation is the date of IRB approval; for multi-site studies, it is the date when the site is activated by the sponsor. The contract received date is the date the draft contract was received by the Institution (PD/PI or institutional contracting official), whichever comes first. The contract execution date is the date it was approved by the institution. For brief description , the title of the trial will suffice; applicants may add further description in addition to the title, as needed.

Liaison to Recruitment Innovation Centers (LRICS)

Delays in recruiting participants to clinical studies are a major barrier to progress in clinical research. In this section, the applicants should describe how they will develop a unit dedicated to supporting the recruitment of trial participants. This unit will need to combine data expertise so that resources like the electronic health record (EHR) can be accessed to identify the number of potential research participants available for any given trial. Additional expertise needed may include the areas of clinical research, patient engagement, communications, cultural competency, and ethics so that potential participants can be notified of research opportunities in an ethical and effective way.

The local recruitment unit will interact with the CTSA Network Recruitment Innovation Centers (RICs). These RICs will provide trial sponsors (initially likely to be the categorical NIH Institutes and Centers) with accurate data on the number of potential research participants that meet the study entry criteria. The data can be used for site selection, recruitment planning and outreach to potential participants. To that effect, the local recruitment unit must enable information extraction from EHR on potential trial participants meeting the specific study entry criteria that can be shared in a de-identified, aggregate format with the RICs. The applicants should describe how this will be done at all clinical spokes affiliated with the CTSA Program Hub, how patient privacy will be safeguarded and how the process complies with regulations pertaining to privacy and human subject protection.

In addition, the local recruitment unit will be involved in informing potential research participants of research opportunities. The applicant will describe how the local recruitment unit will help connect potential participants to active trials in accordance with the Health Insurance Portability and Accountability Act (HIPAA) and consistent with any consent documents used. Potential clinical trial candidates are often informed of research opportunities by their health care provider only. However, applicants may describe more streamlined models that that would entail more direct outreach to potential participants. Until the RICs are operational, the CTSA Program Hubs will support local investigators in estimating the number of potential research participants, and in recruiting them into studies.

Specifics on interactions between the local recruitment units and the future RIC efforts are expected to be defined in the form of joint standard operating procedures once the RIC centers are established. Therefore, applicants should at this time describe in general terms only their capacity to interact with the RICs. However, as noted above, applicants should describe in detail whether and how they can access the EHR locally to aid the estimation of participants who might meet the entry criteria for a study and if so, how they might be informed and recruited. They should describe how they will assist researchers in contacting participants, and how they will consider whether any policy changes are needed at their hub.

The applicant should show as separate columns in the table under Trial Innovation Centers of planned monthly enrollment in a given trial versus the number of patients actually enrolled at the hub. The information can be provided either in two separate tables for combined into one table.

Letters of Support: Only letters of support specific to Network Capacity should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type CTR Core.

Applicants may include up to two optional functions based on specific strengths and needs of the particular proposed CTSA Program Hub. Each proposed optional function will require its own component. Applicants may propose optional functions including, for example, Phase 1 trial units, genomics, phenotyping, biomarkers, drug discovery, preclinical development, imaging, or collaboration with Schools of Veterinary Medicine, rural health/telemedicine and others. Optional functions need to be feasible based upon unique opportunity and substantial prior experience.

These optional functions may also focus on collaborations with other CTSA Program Hubs, for example to evaluate the effect of a new or existing tool or method on clinical and translational research at multiple hubs. Whenever possible, applicants should consider an experimental approach to evaluating innovations. Different components of one CTSA Program Hub, or several collaborating CTSAs could, for example, be randomized or cluster-randomized to the innovative approach, and then prospectively compared to those randomized to standard practice. This will allow for subsequent data-driven decision making.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Optional Functions)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component H. Optional Functions .
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Optional Functions)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Optional Functions)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Optional Functions)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Optional Functions)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch need only be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Optional Functions)

Budget forms appropriate for the specific component will be included in the application package.

Budget Justification: For all tasks, the amount requested must be well justified. The budget justification should list each function and a corresponding justification for the associated costs.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Optional Functions)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed in the Optional Functions component.

Specific Aims: Describe the specific aims to address optional activities in areas of unique strength or opportunity.

Research Strategy: This component allows applicants to propose optional functions for particular strengths and interests. Applicants should describe how CTSA funding will be used to enhance innovation, access and quality in a measurable way.

Letters of Support: Only letters of support specific to Optional Functions should be attached to this section.

Resource Sharing Plan: The Resource Sharing Plan for the CTR Cores should be described under the Administrative Core. Do not include a Research Sharing Plan in the individual CTR Cores.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Inst Career Dev .

Applicants are advised to frame their Career Development cores in the context of the overall Clinical Research Training and Career Development "Ecosystem" of the CTSA Program hubs.

It is critical to follow all Training (T) instructions provided in the SF424 (R&R) Application, with the following additional modifications:

Substitute the term scholars for all references to trainees in the SF424 (R&R) Application Guide, and substitute the term career development for all references to training in the SF424 (R&R) Application Guide.

SF424 (R&R) Cover (Institutional Career Development Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component I: Institutional Career Development Core
• Proposed Project Start/Ending Dates

Project/Performance Site Location(s) (Institutional Career Development Core)

Follow all instructions provided in the SF424 (R&R) Application.

Follow all instructions provided in the SF424 (R&R) Application, with the following additional modifications:

Substitute the term scholars for all references to trainees in the SF424 (R&R) Application Guide, and substitute the term career development for all references to training in the SF424 (R&R) Application Guide.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide an abstract of the career development core. Include the objectives, rationale and design of the research career development program, as well as key activities in the career development plan. Indicate the planned duration of appointments, the projected number of scholars including their levels (i.e., predoctoral, postdoctoral, short-term faculty), and intended scholar outcomes.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Follow all instructions provided in the SF424 (R&R) Application, with the following additional modifications:

The Core Leader and any other individuals whose contributions are critical to the development, management and execution of the Core in a substantive, measurable way (whether or not salaries are reimbursed) should be identified as senior/key persons. These would include co-Leader(s), if applicable, and other Core staff.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the core.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Core Lead may not be the PD/PI of the CTSA application but should work closely with the CTSA leadership to leverage training opportunities and share faculty expertise. The Core Lead will assume the PD/PI role on the KL2 award following a successful review and funding of the U54 application; absent U funding, K awards will not be made.

Do not include proposed mentors (other than senior/key persons) in this section. Biographical Sketches for mentors will be included in the PHS 398 Research Training Program Plan Form, Participating Faculty Biosketches attachment.

Follow all instructions provided in the SF424 (R&R) Application.

Follow the Instructions in the in the SF424 (R&R) Application Guide with the following additional modifications:

• Include all personnel other than the Core Lead(s) in the Other Personnel section, including clerical and administrative staff. Also include proposed salary costs for planned scholars.
• Do not complete the section on Participant/Trainee Support Costs.
• The CTSA Institutional Career Development Program for translational researchers will be programmatically linked, but will have a separate PD/PI when awarded, and a budget based on the number of scholars projected. The recommended number of scholars to budget for in the application is 4 for small hubs (total anticipated CTSA award <$4.5M DC), 6 for medium hubs (total anticipated CTSA award $4.5M-$6M DC), and 9 for large hubs (total anticipated CTSA award >$6M-$7.5M DC).
• If an institution is currently funded under the CTSA Program, and if the number of KL2 scholars currently provided through the CTSA grant is greater than the number recommended in this FOA, then applicants may choose to describe a transition period of up to three years when needed to reduce the number of KL2 scholars. This is to allow for a transition to the new model, and to lessen the impact on ongoing career development. This gives applicants flexibility when budgeting for KL2 scholars within the limit of the Award Budget described in Section II which remains unchanged.
• Alternatively, applicants may request more KL2 scholars than is recommended in this FOA but must justify the higher than recommended number of scholars of up to three years when needed to reduce the number of KL2 scholars. This is to allow for a transition to the new model, and to lessen the impact on ongoing career development. This gives applicants flexibility when budgeting for KL2 scholars within the limit of the Award Budget described in Section II which remains unchanged.
• Alternatively, applicants may request more KL2 scholars than is recommended in this FOA but must justify the higher than recommended number of scholars.
• For each scholar, the following should be budgeted: Salary support will be provided up to $120,000. In general, 9 person-months (75 percent of the KL2 full-time professional effort) must be devoted to the KL2 program, except for those in surgical specialties, which can have less than 9 person-months (75 percent), but no less than 6 person-months (50 percent), protected time for this program, if sufficiently justified and programmatically approved.
• In addition, support may be requested for research and career development activities as detailed below.
• The average total amount budgeted per scholar must not exceed $180,000 in direct costs per year.

Other Direct Costs: The K budget may include funds to support K scholar research projects and career development activities. Applicants may request from $25,000 to $50,000 per year to cover the following expenses: (a) tuition and fees related to career development; (b) research expenses such as supplies, equipment and technical personnel to supplement those provided by the mentor; (c) up to $2,500 for scholar travel to scientific meetings and research training workshops; and (d) statistical services.

In addition, mentor support may include up to $10,000 per year associated laboratory or other research-related expenses. Salary support for mentors excluding laboratory- or research-related expenses is not an allowable budget item.

PHS 398 Research Training Program Plan (Institutional Career Development Core)

The PHS 398 Research Training Program Plan Form is comprised of the following sections:

Training Program

Faculty, Trainees, and Training Record

Other Training Program Sections

Appendix. Note that the Appendix should only be used in circumstances covered in the NIH policy on appendix materials or if the FOA specifically instructs applicants to do so.

Follow all Guide with the following additional modifications:

Particular attention must be given to the required Training Data Tables. Applicants should summarize, in the body of the application, key data from the tables that highlight the characteristics of the applicant pool, faculty mentors, the educational and career outcomes of participants, and other factors that contribute to the overall environment of the program.

Substitute the term scholars for all references to trainees in the SF424 (R&R) Application Guide, and substitute the term career development for all references to training in the SF424 (R&R) Application Guide.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for the Institutional Career Development Core.

Training Program Section

Program Plan

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional instructions:

Proposed Career Development Program.

Describe how scholars will be educated in the human health- and disease-related aspects of their research career development.

Instruction in grant writing, the peer review process, and novel career development opportunities (e.g., optional experiences in industry, community health centers, other CTSA Program Hubs or research institutions, non-governmental organizations) is also encouraged, so that scholars obtain a working knowledge of career options and the steps required to transition successfully to the next stage of their chosen career. Describe how knowledge will be fostered in rigorous research methodology that would help promote best practices among the next generation of researchers for minimizing bias in experimental design and reporting. Describe how flexibility to adapt to individual education needs will be provided.

Applicants should present a broad vision of the workforce needed to drive future innovation and implement effective clinical and translational research. Describe ideas for integrating a team science approach into career development, and for offering a research curriculum aligned to core competencies in translational research. Early exposure to collaboration leveraging disparate areas of expertise may enhance efforts to cultivate a team approach to tackle current challenges facing clinical research. The Institutional Career Development component will provide formal coursework, research experiences, and career guidance to postdoctoral scholars. The CTSA career development environment should serve as a hub for fostering high-impact research careers in translational research.

Harmonizing career development across a CTSA Program Hub requires integrating clinical and translational science across multiple departments, schools, and clinical research institutes in a team science approach to research collaboration. Support for a range of disciplines (including medicine, dentistry, nursing, pharmacy, public health, epidemiology, biostatistics, bioinformatics or bioengineering) should be offered.

Distance training, sharing resources, and reciprocal exchanges of scholars/mentors are encouraged but not required. They can address the research and career guidance needs of scholars and introduce interactive and innovative programs that include real-world exposure to different areas of translational research.

Describe any plans to collaborate with other CTSA Program Hubs. Collaboration in career development and research training initiatives is encouraged. Taking advantage of modern information technology, CTSA Program Hubs should seek opportunities to share methods or online resources, and to disseminate tools.

If clinical trial is proposed, provide documentation of the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the clinical trial, including any feasibility or ancillary study, proposed by Scholar(s) (K12).

Program Evaluation: Applicants are expected to work with a CTSA Program-wide initiative establishing common metrics across the CTSA network.

Scholars Candidates.

If clinical trial is proposed, discuss the potential of prospective Scholars (K12) to organize, manage, and implement the proposed clinical trial, feasibility or ancillary study.

Institutional Environment and Commitment to the Program.

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional instructions:

Institutional Environment and Commitment to the Program: Describe the environment for career development, emphasizing institutional strengths; broadly indicate which disciplines/departments candidates may apply from, quoting any historical data from the previous 5 years (as applicable). The sponsoring institution must assure support for the proposed core including assurance that sufficient time will be allowed for the Core Leader and other faculty to contribute to the proposed program and that there will be protected time for scholars (generally 9-person months, equivalent to 75%) selected for the program.

In demonstrating their institutional commitment, applicants should describe any existing career development activities in translational research currently supported by the institution.

Recruitment Plan to Enhance Diversity: Individuals are required to comply with the instructions for Recruitment Plan to Enhance Diversity as provided in the SF424 (R&R) Application Guide. Applications must include a description of plans to recruit a diverse scholar pool and may wish to include data in support of past accomplishments. Information should be included on both successful and unsuccessful recruitment strategies.

Plan for Instruction in the Responsible Conduct of Research: Individuals are required to comply with the instructions for Plan for Instruction in the Responsible Conduct of Research as provided in the SF424 (R&R) Application Guide.

Progress Report (Renewal Applications Only): Renewal applications must provide a Progress Report on career development activities according to the instructions in the SF424 (R&R) Application Guide

Faculty, Trainees, And Training Record Section

Participating Faculty Biosketches

If the mentor will supervise a Trainee proposing to gain research experience in a clinical trial, provide documentation of his/her expertise, experience, and ability to provide appropriate guidance and help the Scholar to meet the study timelines.

Data Tables

Particular attention must be given to the required Training Data Tables.

Tables 2 and 8C are required for new, renewal, and revision applications. The tables are found at the following link: https://grants.nih.gov/grants/funding/424/datatables.htm

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional modifications:

Study Record: PHS Human Subjects and Clinical Trials Information

DO NOT USE. Attempts to submit a full, detailed study record will result in a validation error.

Delayed Onset Study

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must complete a Delayed Onset Study.

When preparing your application in ASSIST, use Component Type NRSA Training.

It is critical to follow all Training (T) instructions provided in the SF424 (R&R) Application, with the following additional modifications:

The Training Core will offer predoctoral students an orientation to translational science and postdoctoral appointees advanced research training aligned with the CTSA goals of advancing therapeutics (drugs, devices, and preventatives), clinical interventions, and behavioral modifications to improve health. The training component should serve as a pipeline introducing trainees of various disciplines to translational research. A variety of predoctoral training options may be offered at the discretion of the PD/PI including short-term training, combined dual-degree training, intensive year-long training, for health-professional students who wish to interrupt their studies for a year or more to engage in full-time research training before completing their formal training programs

These training tracks serve as a means to attract candidates from multidisciplinary fields and they offer flexibility to meet the research needs of the individual trainees.

Applicants are advised to frame their Institutional Training core in the context of the overall Clinical Research Training and Career Development "Ecosystem" of the CTSA Program hubs.

SF424 (R&R) Cover (Training Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: Title this component J: NRSA Training Core .
• Proposed Project Start/Ending Dates

Project/Performance Site Location(s) (Training Core)

Follow all instructions provided in the SF424 (R&R) Application.

Research & Related Other Project Information (Training Core)

Follow all instructions provided in the SF424 (R&R) Application

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide an abstract of the entire application. Include the objectives, rationale and design of the research training program, as well as key activities in the training plan. Indicate the planned duration of appointments, the projected number of trainees including their levels (i.e., predoctoral, postdoctoral, short-term faculty), and intended trainee outcomes.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Research & Related Senior/Key Person Profile (Training Core)

Follow all instructions provided in the SF424 (R&R) Application, with the following additional modifications:

The Training Core Leader and any other individuals whose contributions are critical to the development, management and execution of the Training Core in a substantive, measurable way (whether or not salaries are reimbursed) should be identified as senior/key persons. These would include co-Leader(s), if applicable, and other Training Core staff.

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the core.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

The Core Lead may not be the PD/PI of the CTSA application but should work closely with the CTSA leadership to leverage training opportunities and share faculty expertise. The Project Lead will assume the PD/PI role of the TL1 award following successful review and funding of the U54 application; absent UL1 funding, TL1 awards will not be made.

Do not include proposed mentors and training faculty members (other than senior/key persons) in this section. Biographical Sketches for mentors and participating faculty will be included in the PHS 398 Research Training Program Plan Form, Participating Faculty Biosketches attachment.

PHS 398 Cover Page Supplement (Training Core)

Follow all instructions provided in the SF424 (R&R) Application.

Training Budget (Training Core)

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

Include all personnel other than the Training PD(s)/PI(s) in the Other Personnel section, including clerical and administrative staff

The NRSA Training Core is an optional part of the CTSA U54 application and will be funded only if the U application is successful. The training component provides stipends at a subsistence allowance to help defray living expenses during the research and clinical training experiences. The allowed number of trainees is 10 for small hubs (total anticipated CTSA award <$4.5M DC), 15 for medium hubs (total anticipated CTSA award $4.5-$6M DC), and 20 for large hubs (total anticipated CTSA award >$6M-$7.5M DC). The amount budgeted per pre-doctoral and post-doctoral trainee must comply with the NRSA stipend levels and allowable costs specified below.

Other Direct Costs: Trainee Travel: Enter the total costs for Trainee Travel, and training related expenses, following the guidance, below:

Although the maximum request is explained under Budget information, the awarded slots will depend upon the scientific and technical merit of the proposed program as determined by scientific peer review and the relevance of the proposed program to programmatic priorities. Further consideration will address program goals and resources, educational resource sharing, and the availability of funds. Applicants should expect that final budgets may be adjusted post-review depending on these factors.

PHS 398 Research Training Program Plan (Training Core)

The PHS 398 Research Training Program Plan Form is comprised of the following sections:

• Training Program
• Faculty, Trainees, and Training Record
• Other Training Program Sections
• Appendix. Note that the Appendix should only be used in circumstances covered in the NIH policy on appendix materials or if the FOA specifically instructs applicants to do so.

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

Particular attention must be given to the required Training Data Tables. Applicants should summarize, in the body of the application, key data from the tables that highlight the characteristics of the applicant pool, faculty mentors, the educational and career outcomes of participants, and other factors that contribute to the overall environment of the program.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for the Training Core.

Provide the rationale for the Training Core and the need for the cross-training proposed. Indicate how the CTSA Training Core will relate to the current training activities at the applicant institution.

Program Plan:

Follow all instructions provided in the SF424 (R&R) Application Guide with the following additional modifications:

Proposed Training:

The PD/PI should describe program activities intended to develop the working knowledge needed for trainees to select among and prepare for the next step in varied research career options (i.e., predoctoral, postdoctoral, short-term faculty) available in the biomedical workforce. For example, programs should provide all trainees with instruction and training in oral and written presentation and in skills needed to apply for individual fellowship or grant support. All postdoctoral trainees should also be provided with instruction in laboratory and project management.

Describe how trainees will be educated in the human health, disease related, and translational aspects of their research training. Describe how training will be fostered in rigorous research methodology that would help promote best practices among the next generation of researchers for minimizing bias in experimental design and reporting. Evidence should be provided that the CTSA supported activities are synergistic (not duplicative) with other funded NIH T32 programs (as applicable).

Recognizing the scope of career opportunities, NCATS strongly encourages the use of Individual Development Plans for trainees, including for example areas such as problem solving, communication, team science, time management, and leadership skills, as well as career guidance. See NOT-OD-14-113 .

Describe ideas for implementing training in team science, and for offering training options that are flexibly adapted to the individual trainee's needs and may include short-term training, dual-degree training, year-off training, and for postdoctoral trainees master’s level training. Curricula should be aligned to translational research core competencies, and career guidance should be provided to trainees. Describe how flexibility to adapt to individual training needs will be provided. Advanced degree offering programs should be described including recruitment and plans for inter-disciplinary exposure.

Training Program Evaluation

NCATS is developing common metrics to measure the impact of the CTSA Program, and will work with successful applicants on their implementation. Describe a plan to review and determine the quality and effectiveness of the training program. This plan should include the metrics to be evaluated (including program activities completed, degree completion (if applicable), publications, fellowships/honors, and subsequent positions) as well as plans to obtain feedback from current and former trainees to help identify weaknesses and to provide suggestions for program improvements. Specified evaluation metrics should be tied to the goals of the program. This should include plans to engage faculty, professional staff, and trainees in educational efforts and obtain feedback from them to help identify weaknesses and to provide suggestions for program improvements (i.e., retention, diversity, and outcomes). Describe plans for tracking career progress among trainees. Identify tools to assess program performance including evaluation of the curriculum, mentors, research training opportunities, and trainees.

Trainee Candidates

Describe, in general terms, the size and qualifications of the pool of trainee candidates (i.e., predoctoral, postdoctoral, short-term faculty) including information about the types of prior clinical and research training and career level required for the program. Do not name prospective Trainees. Describe specific plans to recruit candidates and explain how these plans will be implemented (see also section on Recruitment Plan to Enhance Diversity). Describe the nomination and selection process to be used to select candidates who would be offered admission to the program and criteria for trainees reappointment to the program. Describe a plan to recruit across multiple disciplines including basic science, medicine, social science and allied health.

Institutional Environment and Commitment to the Program: The sponsoring institution must assure support for the proposed Training Core including assurance that sufficient time will be allowed for the Training Core Leader and other Faculty to contribute to the proposed training. Institutions with ongoing research training, student development, or career development programs that receive external funding should explain what distinguishes the proposed Training Core from existing training programs at the same trainee level, how the programs will synergize, if applicable, whether trainees are expected to transition from one support program to another, and how the training faculty, pool of potential trainees, and resources are sufficiently robust to support the proposed training in addition to existing ones.Describe the training environment emphasizing institutional strengths; broadly indicate which disciplines/departments candidates may apply from quoting any historical data from the past 5 years (as applicable). Describe new areas of recruitment leveraging expertise from faculty.

Recruitment Plan to Enhance Diversity: Individuals are required to comply with the instructions as provided in the SF424 (R&R) Application Guide. Applications must include a description of plans to recruit a diverse trainee pool and may wish to include data in support of past accomplishments. Information should be included on both successful and unsuccessful recruitment strategies.

Plan for Instruction in the Responsible Conduct of Research: Individuals are required to comply with the instructions for Plan for Instruction in the Responsible Conduct of Research as provided in Chapter 8 of the SF424 (R&R) Application Guide.

Progress Report (Renewal Applications Only): Renewal applications must provide a Progress Report on training activities according to the instructions in the SF424 (R&R) Application Guide

Faculty, Trainees, And Training Record Section

Data Tables

Particular attention must be given to the required Training Data Tables.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study
All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CTSA Program Hub to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: To what extent does the CTSA application clearly describe and justify their strategic vision to innovate translational research and goals? To what extent do applicants provide a plan to measure these goals?

To what degree do the applicants have a strong record of translational and clinical research with high impact achievements in useful methods and procedures leading to improved diagnoses, treatments, and strategies for disease prevention?

In addition, for applications proposing clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

In addition, for applications proposing clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: To what extent are plans proposed for innovation to improve both educational and research methods and processes, including carefully selected, useful metrics?

Does the hub institution demonstrate its commitment to innovation such as participating in a centralized, streamlined CTSA network, including participating in NIH multi-site trials featuring central Institutional Review Boards and pre-negotiated master subcontracts?

In addition, for applications proposing clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How have the applicants described their specific aims to act as a catalyst for high-quality clinical and translational research, locally and as part of the CTSA network? To what extent are their plans for incorporating local partners and other CTSA Program Hubs in translational research and education realistic and are they likely to succeed?

How are they prepared, where possible, to engage in research across the lifespan and in underserved populations?

To what extent have the applicants described how local and national communities will be integrated throughout all phases of translational science?

To what extent have the applicants described how Community Engagement will be integrated into the leadership, implementation, research and communications strategies at their hub?

To what extent does the plan for informatics coordination include relevant partners? How strong is the plan to use informatics for all stages of translation from support of basic research to knowledge discovery, from integration of medical records to community engagement and education?

To what degree are the plans state of the art for the use of informatics in Community and Collaboration, Translational Endeavors, Research Methods, Hub Research Capacity, Network Capacity and any proposed Optional Functions?

How strong is the focus on interoperability and harmonization among existing informatics platforms? How likely will the plan for management of research data ensure the security of researchers data at participating institutions? How feasible and well managed are the proposed timelines? How strong is the plan to participate in the CTSA informatics network?

In addition, for applications proposing clinical trials

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: To what extent does an integrated program across the local health care delivery system and the translational research enterprise exist? How might this integrated program assist in establishing clinical trial feasibility and improve trial recruitment in an efficient and ethical manner?

To what extent have the applicants been successful in selecting and mentoring doctoral level scientists in preparation for a career in academic medicine or related fields? How have the applicants been able to follow the careers of mentees and have they defined and summarized their successes and failures in this endeavor?

How will this CTSA Program Hub benefit from unique institutional strengths such as human capital, infrastructure, and skillful partner institutions in the support of clinical and translational research and education?

In addition, for applications proposing clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the program proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed program involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

As applicable for the program proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for a component to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the component proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each of the criteria. Scores will be assigned to the named components (Administrative Core, Informatics, Community and Collaboration, Translational Endeavors, Research Methods, Hub Research Capacity, Network Capacity, and Optional Functions) as an aggregate. The aggregate does not need to be strong in all categories to be judged likely to have a major scientific impact. For example, a component that by its nature is not innovative may be essential to advance the field.

Significance

How will the proposed specific aims of the administrative core including organization, governance, collaboration, communication, and succession planning result in successful management of the proposed CTSA Program Hub?

To what extent have applicants provided information related to their capacity to collect metrics measuring impact of their CTSA Program Hub?

To what extent has the applicant described how the interaction between the CTSA Program Hub leadership and its External Advisory Committee will lead to identifying opportunities for improvement and action to mitigate problems identified?

How feasible and likely to be successful are the plans to meet the specific aims with regards to informatics, community engagement, team science and collaboration?

To what extent have the applicants articulated plans to lay the foundation of high quality research by creating and maintaining a skillful translational workforce informed by high quality and innovative biostatistics as well as regulatory and legal experts? Are these plans likely to be successful?

To what degree does the application set forth plans to create and maintain successful pilot translational and clinical studies; where possible, integrate special populations in translational and clinical research; and retain a limited cohort of experienced clinical research professionals to advise and support study-specific staff?

To what extent have the applicants set forth a plan to establish a liaison to Trial Innovation Centers and Recruitment Innovation Centers? How have the applicants demonstrated their commitment to participating in multi-site trials supported by National Institutes of Health Institutes and Centers?

Have the applicants proposed additional functions based upon strengths and interest? How are these extra functions likely to enhance the hub and the CTSA Program in either innovative translational and clinical research or in the education of tomorrow’s investigators?

Investigators

How well-matched are the proposed CTSA Program Hub investigators to continue the gradual transformation of the CTSA Program into a high-performance network marked by not only individual CTSA Program Hub excellence but also by a nimble highly responsive aggregate able to develop, demonstrate and disseminate advances in diagnosis, treatment and prevention of human diseases quickly?

How have hub investigators been successful at innovation in clinical and translational research and in education within the confines of the hub and at the national and international level? To what degree are investigators committed to innovation in process improvement and the use of common metrics in the management (identification of best practices and problems) of hub and network activities?

Innovation

To what extent are the applicants likely to contribute by means of collaboration with other CTSA sites to test innovative ideas in research and education? How does the application reveal a strong track record of innovation and impact in clinical and translational research?

To what extent does the application include plans to expand translational research to include young or older persons or other special populations?

To what extent are innovative methods evident, such as experimental approaches to identify best practices in both translational research and workforce education? To what degree do the plans include not only developing innovations but also using innovations made by others to demonstrate utility and to ultimately disseminate successful innovations?

Approach

How strong are the plans to use informatics in support of the entire spectrum of translational research? How likely to be successful are the applicants' plans to integrate data from different sources such as sensors, mobile platforms, EHR, clinical databases, research datasets, patient reported outcomes and data from other sources? To what extent do the applicants propose innovate informatics solutions (such as discovery informatics, human-computer interaction, sensors and mobile platforms, or interactive environments and games) in support of translational research, training or education? To what degree are bioinformatics or informatics innovations proposed in support to the broad range of translational research, education and training functions across the CTSA Program Hub?

How robust is the plan to establish and sustain a research data warehouse? How strong is the data warehouse team? To what extent do the applicants provide a robust quality management plan for the research data warehouse? How strong are the plans to recruit, train and support the members of a research data warehouse team? How likely are they to contribute to best practices in research data warehousing across the CTSA network or with other initiatives such as PCORNet? How strong are the plans to use standard terminologies, or if absent, to what extent are the applicants committed to developing and then broadly sharing missing standards? To what extent will applicants be able to incorporate new standards into their terminology? How strong is the ability to handle diverse query types? How robust is the current capacity to handle queries, and what is the ability to scale up? How likely is it that the applicants will be able to execute a query to determine the number of potential participants meeting study entry criteria? (presume a query for the number of potential participants meeting study entry criteria with regards to age, primary and secondary diagnoses (ICD), current medications and a commonly used laboratory measure)? To what extent can the applicants query the EHR across the multiple components of their institution, and their partners (including outpatient clinics)?

To what extent is an appropriate user-friendly data management system proposed with training on its use and basic support? How are challenges and alternative approaches addressed?

To what extent does the application describe a practical means to engage the variety of local communities with an interest in clinical and translational research, such as patients, clinicians, advocacy groups, and others? To what extent does the application include a description of approaches or strategies to engage communities? To what extent does the application describe how they will use CTSA resources to develop best practices, informational material and consultations on how to engage communities as strong, well prepared and active partners around specific projects?

To what extent are the applicants committed to using common metrics to identify best practices and opportunities for improvements at both local hubs and across the CTSA network?

How will the proposed approaches to the overarching, high-priority functions and specific functions contribute to efficient, high quality clinical and translational research and training?

To what extent will this applicant support the development of a skillful translational science workforce? To what extent is there a commitment to refinement of the academic reward system toward the recognition of translational researchers and team scientists?

For the overarching, high priority functions (B and C in table Section IV), to what extent has the applicant organized resources and staffing in a realistic fashion? To what extent are resources proposed well justified?

For the specific functions (D-G in table Section IV), to what extent has the applicant organized proposed resources and staffing in a realistic fashion? To what extent are resources proposed well justified?

To what extent are the optional functions well justified? How well do they represent a unique opportunity at the hub? To what extent is an experimental approach to evaluating innovations in the optional function proposed and appropriate?

How well do the applicants identify obstacles and propose solutions to the creation of a high performance CTSA network capable of quickly and efficiently fielding multi-site clinical trials in response to NIH Institutes and Centers invitations?

Environment

To what extent is the inclusion of all partner institutions well justified and sound? How likely is the collaboration(s) to be vigorous, balanced and productive?

How likely is this CTSA applicant committed to being a constructive member of the overall CTSA network, and an active and constructive contributor to the CTSA Steering Committee, Domain Task Forces and NCATS deliberations?

As applicable for the project component proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Reviewers will provide an overall impact score to reflect their assessment of the likelihood that the proposed career development program will prepare individuals for successful, productive scientific research careers and thereby exert a sustained influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of the merit of the career development program, and give a separate score for each. When applicable, the reviewers will consider relevant questions in the context of proposed short-term career development. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Career Development Program and Environment

Does the proposed program clearly outline a plan to recruit and develop well-qualified junior investigators for successful careers as biomedical or clinical researchers? Is there evidence of an adequate pool of potential scholars who could benefit from receiving career development support?

Are the content and duration of any proposed didactic, career development-related, and research-related activities of the program appropriate? Are appropriate timelines indicated for career progression and transition to independence?

Does the institutional environment (e.g., research facilities and other relevant resources) in which the program will be conducted contribute to the probability of success? Does the proposed career development program benefit from unique features of the scientific environment, subject populations, or employ useful collaborative arrangements? Is the institutional commitment to the proposed program appropriate?

If multiple sites are participating, is this adequately justified in terms of the career development and research experiences provided?

Is there sufficient assurance that the required effort of the Core Lead, mentors and scholars will be devoted directly to the career development and related activities? When applicable, is there adequate documentation describing the responsibilities of the advisory committee with regard to the provision of input, guidance and oversight of the program?

To what extent is the proposed research education curriculum aligned with core competencies in translational research?

To what extent are there innovative or non-traditional methods or educational opportunities?

Do the Core Lead and Research Administrator (if applicable) have the experience to develop, direct and administer the proposed program? Does the leadership team bring complementary and integrated expertise to the program? Is there evidence that an appropriate level of effort will be devoted by the program leadership to ensure program objectives? Are the research qualifications, scientific stature, previous leadership and mentoring experience, and track record(s) appropriate for the proposed career development program? Are the Core Lead(s) currently engaged in research relevant to the scientific area of the proposed program?

For applications designating multiple Core Leads:

To what extent is a strong justification provided that the multiple PD/PI leadership approach will benefit the career development program and the scholars?

To what extent is a strong and compelling leadership approach evident, including the designated roles and responsibilities, governance, and organizational structure consistent with and justified by the aims of the career development program and the complementary expertise of the PDs/PIs?

Mentors

Do the mentors have appropriate expertise and experience, as well as track records of past mentoring and training? Are the quality and extent of the mentors roles in providing guidance and scientific advice to the scholars acceptable? Are the mentors currently engaged in relevant research?

Candidates/Scholars

Is a recruitment plan proposed with strategies likely to attract high quality, diverse scholar candidates?

Are there well-defined and well justified recruitment and selection strategies? Is there evidence of a sufficiently large, competitive scholar pool to warrant the proposed size of the career development program?

Are the content, phasing, and proposed duration of the career development plan appropriate for achieving scientific independence of the scholar candidates? What is the likelihood that the career development plan will contribute significantly to the scientific development of the scholars? Does the plan for selection of the scholars include all of the eligibility criteria stated in the FOA?

To what extent is there a description of the process to provide personalized career guidance? Are the content, training track, and proposed duration of the individual (career) development plan appropriate for achieving scientific independence? What is the likelihood that the personalized plan will contribute significantly to the scientific development of the scholars?

Training Record

Is there evidence of a successful past training record of the Core Lead and mentors, including the success of former scholars in seeking independent support and establishing productive scientific careers? Does the program have a rigorous evaluation plan to assess the quality and effectiveness of the career development plan?

To what extent have tools been identified to assess program performance including evaluation of the curriculum, diversity, mentors, research training opportunities, and scholars? Does the program have a rigorous evaluation plan to assess the quality and effectiveness of the program objectives?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Inclusion of Women, Minorities, and Children

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Vertebrate Animals

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Biohazards

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Recruitment Plan to Enhance Diversity

Peer reviewers will separately evaluate the recruitment plan to enhance diversity after the overall score has been determined. Reviewers will examine the strategies to be used in the recruitment and retention of individuals from underrepresented groups. The plan will be rated as ACCEPTABLE or UNACCEPTABLE, and the consensus of the review committee will be included in an administrative note in the summary statement.

Training in the Responsible Conduct of Research

All applications for support under this FOA must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). Taking into account the specific characteristics of the career development program, the level of scholar experience, and the particular circumstances of the scholars, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - Does the plan satisfactorily address the format of instruction, e.g. lectures, coursework and/or real-time discussion groups, including face-to-face interaction? (A plan involving only on-line instruction is not acceptable.); 2) Subject Matter Does the plan include a sufficiently broad selection of subject matter, such as conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics? 3) Faculty Participation - Does the plan adequately describe how faculty will participate in the instruction? For renewal applications, are all career development faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period named in the application? 4) Duration of Instruction - Does the plan meet the minimum requirements for RCR, i.e., at least eight contact hours of instruction? 5) Frequency of Instruction Does the plan meet the minimum requirements for RCR, i.e., at least once during each career stage (undergraduate, post-baccalaureate, predoctoral, postdoctoral, and faculty levels) and at a frequency of no less than once every four years?

For renewal applications, does the progress report document acceptable RCR instruction in the five components described above? Does the plan describe how participation in RCR instruction is being monitored? Are appropriate changes in the plan for RCR instruction proposed in response to feedback and in response to evolving issues related to responsible conduct of research?

Plans and past record will be rated as ACCEPTABLE or UNACCEPTABLE, and the summary statement will provide the consensus of the review committee.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including (1) the Select Agent(s) to be used in the proposed research, (2) the registration status of all entities where Select Agent(s) will be used, (3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and (4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment that the proposed training component will prepare individuals for successful and productive scientific research careers. The environment, leadership and mentors, and the evaluation plan will all factor into the overall impact score.

Scored Review Criteria - NRSA Training

Reviewers will consider each of the review criteria below in the determination of the merit of the training program, and give a separate score for each. When applicable, the reviewers will consider relevant questions in the context of proposed program plan. An application does not need to be strong in all categories to be judged likely to have major scientific impact.

Training Program and Environment

To what extent are the research facilities and research environment conducive to preparing trainees for successful careers as biomedical research scientists?

To what extent are the objectives, design, and direction of the proposed research training program likely to ensure effective training?

To what extent do the courses, where relevant, and research experiences provide opportunities for trainees to acquire state-of-the-art scientific knowledge, methods, and tools that are relevant to the goals of the training program?

To what extent does the program provide appropriate inter- or multidisciplinary research training opportunities?

To what degree is the proposed training program likely to ensure trainees will be well prepared for research-intensive and research-related careers?

To what degree is the level of institutional commitment to the training program, including administrative and research training support, sufficient to ensure the success of the program?

Has it clear been how the proposed training program is distinguished from other externally funded training programs at the institution?

Specific to this FOA:

To what extent are the objectives of the program clearly explained and reflective of the institutional strengths?

To what degree is the CTSA Program Hub including the research environment conducive to preparing trainees for successful careers as translational scientists? Is the NRSA Training component sufficiently integrated with the CTSA scientific vision?

To what extent is the institutional commitment to the proposed program appropriate? If multiple sites are participating, are the trainee appointments equitable across the sites and if not, is the distribution justified in terms of the research training experiences provided? Is the NRSA Training component integrated with other institutional training (NRSA) programs at the institution? Is the NRSA Training component sufficiently integrated with the CTSA scientific vision? Does the applicant indicate appropriate institutional and departmental commitment to the program reflected in recruitment efforts, educational resources and equipment, and faculty? Is there sufficient assurance that the required effort of the Program Lead, mentors, and trainees will be devoted directly to the research training and related activities?

How strong are the applicant's plans to work with other CTSA sites on shared training opportunities and on harmonization in education and training?

To what degree are the conceptual elements of team-based research included in the scope of program activities?

To what extent are appropriate advanced degree granting programs offered? Does the proposed program clearly outline a plan to recruit candidates across multiple disciplines ranging from basic science to social science including medicine and allied health fields?

To what degree does the curriculum offer novel learning models to meet the needs of trainees? Will the curricula provide appropriate training in clinical and translational research relevant to a broad range of specialties and with appropriate emphasis on the needs of team science?

To what degree does the curriculum offer innovative methods or access to non-traditional learning experiences?

Training Core Lead(s)

To what extent does the Training Core Lead have the scientific background, expertise, and administrative and training experience to provide strong leadership, direction, management, and administration of the proposed research training program?

To what extent does the Training Core Lead plan to commit sufficient effort to ensure the program’s success?

For applications designating multiple Core Leads:

To what extent is a strong justification provided that the leadership approach of the multiple Core Leads will benefit the training program and the trainees?

To what extent is a strong and compelling leadership approach evident, including the designated roles and responsibilities, governance, and organizational structure consistent with and justified by the aims of the training program and the complementary expertise of the Core Leads?

Preceptors/Mentors

To what extent are sufficient numbers of experienced preceptors/mentors with appropriate expertise and funding available to support the number and level of trainees (including short-term trainees, if applicable) proposed in the application?

To what extent do the preceptors/mentors have strong records as researchers, including recent publications and successful competition for research support in areas directly related to the proposed research training program?

To what extent do the preceptors/mentors have strong records of training individuals at the level of trainees (including short-term trainees, if applicable) proposed in the program? Are appropriate plans in place to ensure that preceptors lacking sufficient research training experience are likely to provide strong and successful mentoring?

Trainees

To what degree is a recruitment plan proposed with strategies likely to attract well-qualified candidates for the training program?

To what degree is there a competitive applicant pool of sufficient size and quality, at each of the proposed levels (pre-doctoral, postdoctoral and/or short-term), to ensure a successful training program?

To what degree are there well-defined and justified selection and re-appointment criteria as well as retention strategies?

Training Record

How successful are the trainees (or, for new applications, other past students/post-doctorates in similar training) in completing the program?

To what degree has the training program ensured that trainees are productive (or, for new applications, other past students/post-doctorates in similar training) in terms of research accomplishments, publication of research conducted during the training period, and subsequent training appointments and fellowship or career development awards?

How successful are the trainees (or, for new applications, other past students/post-doctorates in similar training) in achieving productive scientific careers as evidenced by successful competition for research science positions in industry, academia, government or other research venues; grants; receipt of honors, awards, or patents; high-impact publications; promotion to scientific leadership positions; and/or other such measures of success?

To what extent do trainees subsequent positions in industrial, academic, government, non-profit, or other sectors benefit from their NRSA-supported research training and directly benefit the broader biomedical research enterprise?

To what extent does the program propose a rigorous evaluation plan to assess the quality and effectiveness of the training? Are effective mechanisms in place for obtaining feedback from current and former trainees?

For applications that request short-term research training positions, is there a record of retaining health professional trainees in research training or other research activities for at least two years?

To what extent does the evaluation plan describe strategies to engage current and former trainees to assess the quality and effectiveness of the program objectives?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Inclusion of Women, Minorities, and Children

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Vertebrate Animals

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Biohazards

Generally, not applicable. Reviewers should bring any concerns to the attention of the Scientific Review Officer.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Recruitment & Retention Plan to Enhance Diversity

Peer reviewers will separately evaluate the Recruitment Plan to enhance diversity after the overall score has been determined. Reviewers will examine the strategies to be used in the recruitment and retention of individuals from underrepresented groups. The plan will be rated as ACCEPTABLE or UNACCEPTABLE, and the consensus of the review committee will be included in an administrative note in the summary statement.

Training in the Responsible Conduct of Research

All applications for support under this FOA must include a plan to fulfill NIH requirements for instruction in the Responsible Conduct of Research (RCR). Taking into account the specific characteristics of the career development program, the level of trainee experience, and the particular circumstances of the scholars, the reviewers will evaluate the adequacy of the proposed RCR training in relation to the following five required components: 1) Format - Does the plan satisfactorily address the format of instruction, e.g. lectures, coursework and/or real-time discussion groups, including face-to-face interaction? (A plan involving only on-line instruction is not acceptable.); 2) Subject Matter Does the plan include a sufficiently broad selection of subject matter, such as conflict of interest, authorship, data management, human subjects and animal use, laboratory safety, research misconduct, research ethics? 3) Faculty Participation - Does the plan adequately describe how faculty will participate in the instruction? For renewal applications, are all career development faculty who served as course directors, speakers, lecturers, and/or discussion leaders during the past project period named in the application? 4) Duration of Instruction - Does the plan meet the minimum requirements for RCR, i.e., at least eight contact hours of instruction? 5) Frequency of Instruction Does the plan meet the minimum requirements for RCR, i.e., at least once during each career stage (undergraduate, post-baccalaureate, pre-doctoral, postdoctoral, and faculty levels) and at a frequency of no less than once every four years?

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NCATS Office of Science Review in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate NCATS Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Policies consistent with goals for resource, data sharing, and sharing of software.
• Programmatic priorities, including but not limited to geographic distribution of CTSA Program Hubs and access to special populations.
• NCATS may fund a UL1 only, or a UL1 & KL2, or a UL1 & TL1, or a UL1 & KL2 & TL1 depending on the scientific and technical merit of the application components.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining approaches, designing, implementing, and setting milestones for advancing translational and clinical research and training
• Ensuring all participating institutions are fully integrated into the CTSA Program Hub
• PD(s)/PI(s) has ultimate responsibility for implementing the activities at the CTSA Program Hub
• Management, implementation, and tracking of the pilot project program
• Ensuring informatics coordination and data exchange to facilitate translational research, compatibility of research systems with broadly accepted content and technical standards including those adopted by the Department of Health and Human Services for health care and public health operations, and compatibility with NIH Institute and Center endorsed common data elements
• Implementation of a data security plan at all participating institutions that ensures the security of research data on all studies involving human subjects
• Maintaining visibility of scientists and resources of CTSA institutions to facilitate collaboration
• Implementation of a plan to create and maintain a broad culture of responsibility for safe and ethical conduct of human subjects research at all participating institutions, which ensures scientifically, and ethically flawed studies are not conducted, enrollment is tracked, and futile studies are closed in a timely manner, workflow for conduct of clinical and translational research is efficient, prompt analysis of results, and dissemination of those results
• Implementation of tracking processes, metrics, and milestones including some metric common to the hubs participating in the CTSA Program
• Provision of disease-agnostic support to translational and clinical researchers. The support must facilitate the participation of local investigators in national networks and multi-site studies, particularly those supported by NIH
• Establishment of career development opportunities that encourage new investigators to work in clinical and translational science
• Implementation of the proposed educational programs in collaboration with other hubs of the CTSA Program, and innovative research training and career development programs activities and assessment of their effectiveness
• Effecting steps toward implementation of the agreed-on policies, procedures, best practices, or other measures established by NCATS
• Provision of information to the NIH Program Officer and the NIH Project Coordinator concerning progress
• Support of CTSA network activities
• Principal investigators and key personnel as appropriate are expected to participate in annual meetings

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIH Project Coordinators (PC) will:

• Provide substantial programmatic involvement that is above and beyond the normal stewardship role in awards.
• Cooperation or coordination with, or assistance to, awardees in performing project activities, e.g., coordination of research networks; coordinating access to NIH supported research resources; identifying other researchers/resources for the projects
• Participation on steering and operations committees as a voting member or in other functions responsible for helping to guide the course of long-term projects or activities; e.g., annual meetings
• No involvement in normal program stewardship
• Not attending peer review meetings of renewal or revision applications unless an NCATS waiver is obtained per NCATS procedures for management of concern about bias
• Provision of a broad overview of the value provided by the awardee as measured by its achievement of its stated aims, the significance of its innovations and deliverables, and its metrics for application of its strengths to the transformation of clinical and translational research within its hub
• Assessment of the awardee’s overall participation in and contributions to the CTSA Network and its support for development and implementation of best practices, policies, and procedures
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Additionally, an NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIH Program Official stewardship includes:

• Enforcement of general statutory, regulatory, or policy requirements
• Approval of awardee plans prior to award and review of performance after completion
• Evaluation of progress by reviews of technical or fiscal reports, by program visits, or with external consultants, to determine that performance is consistent with objectives, terms and conditions of the award
• Technical assistance requested by awardees, or correcting programmatic or financial deficiencies in awardee performance
• Scientific and technical discussions with awardees, or actions to facilitate or expedite interactions between awardees; e.g., organizing and holding meetings of investigators

Areas of Joint Responsibility include:

None; all responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Other Reporting Requirements

• The institution must submit a completed Statement of Appointment (PHS Form 2271) for each scholar or trainee appointed or reappointed to the training grant or career development award. Grantees must submit the PHS 2271 data electronically using the xTrain system. More information on xTrain is available at xTrain (eRA Commons). An appointment or reappointment may begin any time during the budget period, but not before the budget period start date of the grant year.
• A notarized statement verifying possession of permanent residency documentation must be submitted with the Statement of Appointment (Form PHS 2271). Individuals with a Conditional Permanent Resident status must first meet full (non-conditional) Permanent Residency requirements before receiving support.
• Termination Notice: Within 30 days of the end of the total support period, the institution must submit a Termination Notice (PHS Form 416-7) via xTrain for each scholar or trainee appointed for eight weeks or more.

For awards involving postdoctoral NRSA training through a TL1, a completed Payback Agreement Form (PHS 6031) must be submitted for each postdoctoral trainee in his or her first 12 months of support.

Trainees with service payback requirements must notify the NIH of any change in address and submit Annual Payback Activities Certification Forms (PHS 6031-1) until the payback service obligation is satisfied.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Mary E. Purucker, M.D.
National Center for Advancing Translational Services (NCATS)
Telephone: 301-435-0741
Email: [email protected]

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: [email protected]

Irene Haas
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301- 435-0836
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.