Required Application Instructions

It is critical that applicants follow the 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). 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

Translating biomedical discoveries into clinical applications is essential to improving human health. It is also a complex process with high costs and substantial failure rates. These failures can result in delays of years or decades before improved patient outcomes result from discoveries in biomedical research. The Clinical and Translational Science Award (CTSA) hubs promote advances in translational research and training at participating medical research institutions. This funding opportunity announcement (FOA) will enable innovative collaborations among CTSA hubs to overcome system-wide barriers to translational effectiveness.

The scientific and operational issues which underlie most translational inefficiency are not specific to a particular disease, discipline, institution, or geographic locale. Rather, they are systematic issues, which require systematic and generalizable solutions. Further, every stage of the translational process, from target validation through intervention development to public health benefit assessment, is currently fraught with ineffectiveness and in need of bold, innovative new solutions. There is therefore a corresponding need for bold and innovative new experimental approaches to identifying such solutions. NCATS' catalysis of the development, demonstration, and dissemination of innovations across the spectrum of translational science will advance its mission to transform the effectiveness of translation of discoveries from the laboratory, clinic, and community into tangible benefits to human health.

This FOA is one of several sequential steps being taken by NCATS to evolve the CTSA program to augment its ability to, as suggested by a recent Institute of Medicine program report (http://www.iom.edu/Reports/2013/The-CTSA-Program-at-NIH-Opportunities-for-Advancing-Clinical-and-Translational-Research.aspx), enhance the transit of therapeutics, diagnostics, 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 .

Individual CTSA hubs, and more recently groups of hubs, have developed and demonstrated the utility of innovations that improve the efficiency and effectiveness of many aspects of translational research and training. The diversity of CTSA hubs, and their multiplicity nationwide, suggests that fostering cross-CTSA innovation development and implementation could transform the nation's translational effectiveness in unprecedented ways. This FOA therefore seeks to encourage all CTSA hubs to collaboratively conceptualize, develop, and implement multi-site innovative experimental approaches that overcome translational barriers in science, operations, and training.

We expect that, collectively, the projects funded under this FOA will have a transformative impact on the nation's translational science enterprise.

This FOA aims to support applications for innovative collaborative investigations (involving three or more CTSA sites) into improvements of the methods of translational research, at any step in the translational spectrum (T1-T4). It is anticipated that the combined effort of three or more CTSA hubs in flexible networks will substantially enhance the effectiveness of the CTSA consortium to address high priority translational research questions. This FOA therefore aims to support innovative and collaborative experimental translational research projects carried out in the CTSA consortium that have the following characteristics:

First, such projects should develop a new technology, method, or approach that addresses a general roadblock in science and/or operations that limits the efficiency and effectiveness of translation. As defined at NCATS, translation is the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public - from diagnostics and therapeutics to medical procedures and behavioral changes. This FOA also supports innovative approaches to training or community/patient engagement that are focused on improving translation.

Second, such projects should demonstrate in one or more use cases whether the tool, method, or approach is effective in accelerating translation, utilizing clear and meaningful metrics and outcomes, when implemented across multiple CTSA hubs.

Third, such projects should advance collaboration, building on existing strengths and resources of individual CTSA hubs. Investigators who are not affiliated with a CTSA hub, but wish to bring an innovative project to the CTSA consortium, can participate in collaboration with a CTSA investigator. Whenever possible, projects should include partnerships between CTSA hubs and external stakeholders such as industry or patient organizations. This is desirable so that the partners can mutually leverage resources, assure meaningful intervention approaches, and increase the likelihood of successful hand-off to the private sector when appropriate.

Fourth, what constitutes success of the proposed project can be defined and measured.

Some examples of such opportunities include but are not limited to:

• Development and implementation of innovative community engagement methods and technologies that demonstrably increase the efficiency and effectiveness of intervention development and deployment, and measurement of their effects on improving health outcomes. Community engagement should be defined broadly to include local and distributed, physical and virtual communities. Research aimed at engaging minority, vulnerable, or other understudied populations in translational research is one area of particular interest.
• Improving the consent process, for example simplifying and reducing the length of the consent forms without sacrificing content; ensuring that the consent form is commensurate with potential participants needs and is culturally sensitive; making the consent process more user-friendly through the use of visual aids or recorded video; in multi-site research, providing similar information across investigators and sites.
• Educating and training the translational research workforce through collaborative initiatives across multiple CTSA hubs that leverage local strengths, using innovative features such as shared, online resources, individualized training with focus on competencies rather than degrees, training in multi-disciplinary team science, regulatory science, entrepreneurship and experiential learning experiences, for example through externships in industry, regulatory agencies, or nonprofit organizations.
• Developing mechanisms for CTSA-catalyzed networks to identify and fast-track particularly promising translational research projects, thereby reducing the time required for intervention development or demonstration of unfeasibility.
• Adapting technology and methodology that are shown to be successful in other domains to address challenges in clinical and translational research.
• Fostering innovative multi-disciplinary collaborations that bring together new types of teams to solve particular clinical and translational research problems.
• Innovative clinical research studies or trials that use mobile technology and web- or phone- based communication to obtain information such as patient reported outcomes and remote biological measures.
• Innovative clinical research designs, such as adaptive designs, serial n of 1 design, or other approaches to small populations, which could overcome some of the challenges in evaluating interventions.
• Innovative approaches to the implementation of precision medicine
• Innovative methodologies that address translational research roadblocks specific to pediatric, geriatric, or other populations throughout the lifespan - e.g., new ways to develop outcome measures or validate biomarkers relevant to those populations, and enhancing lifestage-specific investigator training.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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)
• Eligible Agencies of the Federal Government
• 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.
Applications must involve investigators from at least 3 CTSA hubs. Each hub must have an active CTSA Award (U54) as of the due date of the application.
The PD/PI, or contact PD/PI in applications using the multiple PD/PI option, must be employed by an Institution with an active CTSA Award (U54). For the Collaborative Innovation Awards (PAR-15-173 and PAR-15-172) the PD/PI, or contact PD/PI in applications using the multiple PD/PI option, must be employed by an Institution with an active CTSA Award (U54), or by a partner institution as identified in the application for the active CTSA award.

Investigators who are not employed by an institution with an active CTSA Award or partner Institution but who wish to bring an innovative project to the CTSA consortium, can co-direct a project in partnership with a CTSA investigator using the multiple PD/PI option.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. 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.

All page limitations 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 an application to this FOA.

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

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

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

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

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

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

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

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

Specific Aims: Briefly state the specific aims of the project indicating how the project will contribute to advancing translational science.

Research Strategy: This section should include:

A statement of the translational science problem being studied, and its significance

A description of and rationale for the proposed innovation. If successful, how would the proposed innovation transform some aspect of translational science?;

A description of the overall strategy and methodology used to accomplish the goals and specific aims of the project. The description should address the following:

Collaboration: Applicants should describe how their project will build on the existing strength of the CTSA consortium, and involve at least three CTSA hubs who collaborate on a translational research project. Applicants should describe their plans and timeframe for how multiple CTSA hubs will participate in this research, identifying those responsible for various efforts, declared milestones, metrics, individual responsibilities, and plans for dissemination of research results.

Innovation: Applicants should explain how their project is innovative. When no available tool or method is suitable, the project may include the development of a novel tool or method approach. When suitable tools or methods exist, applicants should describe their choice of approach, and how the existing tools are used in an innovative manner to advance translation. Applicants should discuss how the project might open a new avenue of translational research, or might be a systematic improvement over the current methods used in translational research. They should note whether the proposed research is an extension of active area of research or a new project for the investigators.

Translation: As applicable to the specific project, applicants should describe:

how the proposed collaborative project, if successful, will have impact on human health or will result in an intermediate outcome linked to health impact; how the innovation proposed in research methods will lead to improvements in the identification, testing, and dissemination of potentially useful means of prevention, diagnosis, and treatment of human disease; or how innovation in the training of the next generation of translational scientists will impact the field of translational science.

Applicants should specifically describe how their project can be generalized to other settings.

Partnership: There should be a description of any partnerships, such as other clinical sites, those with patient organizations, or partners in the private sector in the area of diagnostics, therapeutics or preventive measures. Applicants should discuss necessary engagement with relevant communities such as the public at large, with relevant patient communities, or with underserved communities. This engagement should occur in all phases of the project and include pre-study discussions, ongoing involvement, updates, and ultimately dissemination of results.

Barriers: Applicants should identify any perceived clinical or scientific barriers or ethical issues and solutions proposed.

Defining success: Applicants should define success for the proposed project and how it can be measured.

For projects that involve clinical research, applicants should describe how IRB approval and monitoring will be streamlined, e.g. by the use of a single IRB or IRB or record.

Letters of Support: Each collaborating investigator should include a letter of support from the PD/PI of the U54 CTSA hub that they are associated with. For multiple investigators from the same CTSA hub, one letter of support from the CTSA PI is sufficient. Where relevant, include letters of support or other documentation of partnerships with the private sector (e.g., patient groups and/or industry), subcontractors, consultants, and/or other providers of personnel and facilities. For drug or device trials, provide evidence that the study drug or device will be available in sufficient quantities to ensure study feasibility. If applicable, letters from authorized Institutional officials agreeing to the proposed single IRB plan should also be included.

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:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Plans for dissemination of the results of the project to the CTSA program, and more broadly to the translational science community are expected to be included.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

For applications that propose a clinical trial, the following items should be included in the appendix:

The protocol synopsis, which should not exceed 5 pages, including the following:

• Study objectives (primary, secondary, exploratory) and outcome measures
• Study design
• A description of the intervention to be tested (if applicable)
• Sample size, if not described in Protection of Human Subjects
• Study population (with key inclusion/exclusion criteria),
• Recruitment plan,
• Study procedures and evaluations, including safety assessments
• Overall study duration and duration of participant involvement.
• Process to be used for obtaining informed consent
• Draft data management plan
• Draft quality management plan
• Draft laboratory plan, including specimen handling, storage, tracking and processing
• Milestone plan for clinical study progress, including recruitment goals, interim analysis, data and safety monitoring

At the time of grant submission, applicants must provide documentation from the FDA providing information on one of the following three scenarios:

(A) The protocol has been submitted under an IND in effect and the IND/IDE is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.

(B) The protocol has been submitted under an IND/IDE and is on full or partial hold. Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations.

(C) The protocol is exempt from an IND/IDE. Under this scenario applicants must provide a copy of the exemption letter from the FDA.

At the applicant's discretion, the following optional elements may also be provided in the appendix:
Non-referenced or non-published, non-standardized clinical assessments and data collection tools.
Investigator Brochures, see 21 CFR 312.23 (a)(5) for format Clinical pharmacology justifying the proposed dosing regimen

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.

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

Part I. Overview Information contains information about Key Dates. 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.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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.

Important reminders:

All PD(s)/PI(s) 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. See Section III of this FOA for information on registration requirements.

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. 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 NCATS. Applications that are incomplete and/or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow our Post Submission Application Materials 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.

This FOA is intended to enable innovative, experimental approaches to overcome system-wide barriers to translation via collaborations among investigators from three or more CTSA hubs.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project 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).

For this particular announcement, note the following: 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? Does the proposed project answer an important translational research question, or does it address a critical gap in translational science? If the project succeeds, will it have a transformative effect on some domain of translational science?

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 the 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? Does the project involve investigators from at least three different CTSA hubs? Does each of the collaborators make a significant contribution to the overall project? Do the applicants leverage partnerships? If so, do the partners play a substantial role, and is there evidence of commitment and support from the prospective partners?

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? Does the application describe the innovative use of an existing approach, methodology, instrumentation, or intervention? Will the results be generalizable to translational research challenges across multiple CTSA hubs, as well as the broader translational research community?

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? Are there plans for engaging partners in next steps, or is there a hand-off plan? Have the applicants considered and addressed potential barriers to success, and discussed contingency plans and described alternative approaches?

Does the proposed project build on an existing discovery or development, and does it have the potential to demonstrate if such an innovation is effective when applied to translational research? Have the applicants presented a realistic plan to measure the success of the proposed project? Have the applicants presented a realistic plan to disseminate the results of the project throughout the CTSA consortium?

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? Is there a description for using a single IRB or IRB or record, and is commitment to this plan demonstrated by letters from all relevant Institutional Officials?

In addition, for applications proposing clinical trials: Does the application adequately address the following, if applicable:

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?

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? Does the project build on the existing strengths and resources of the CTSA program, and at the individual investigators Institutions and CTSA hubs?

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 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.

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 project 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.

Not Applicable

Not Applicable

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.

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, including dissemination of the results of the project to the translational science community; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCATS, 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 to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.

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.

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.

Additionally, ICs may specify any special reporting requirements for the proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If the proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. 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.nig.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).

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.

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 as a whole, 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:

• The Program Director/Principal Investigator will have the primary responsibility to define research objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusion of their studies and for providing overall scientific and administrative leadership for the Research Project.
• The PD/PI will oversee all aspects of the organization and execution of the studies outlined in the application and approved by NCATS after peer review.
• Awardees have primary and lead responsibilities for the project as a whole, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the primary leadership committee.
• Putting all study materials and procedure manuals into the public domain. Awardees are expected to publish and publicly disseminate results, data, and other products of the study, concordant with governance policies and protocols. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the NCATS/NIH.
• Obtaining prior written approval of the NCATS Grants Management Specialist in consultation with the NCATS Program Officer for any change in any of the key personnel identified in the Notice of Grant Award.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

An NCATS Project Scientist will have substantial programmatic involvement that is above and beyond the typical stewardship role in other awards, as described below. In addition to the Project Scientist, an NCATS Program Official will be responsible for programmatic stewardship of the award and will be named in the award notice.

NCATS Project Scientist will:

• Have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NCATS staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.
• Serve as a resource to provide scientific/programmatic support during the accomplishment of the research by participating in the design of the activities, advising in the selection of sources or resources (e.g., determining where a particular reagent can be found), provision of research resources and reagents available from NCATS grantees and contractors, or other CTSA sites, advising in management and technical performance, or participating in the preparation of publications.
• If Award involves a clinical study, oversee the adequacy of adverse event management and reporting, and have regular communications with the PD/PI and study team, which may include attendance at the DSMB and related committee meetings. Review and monitor progress of inclusion of women and minorities in the clinical trial
• Review the progress of each participating facility, through consideration of the annual reports, site visits, screening logs, etc.
• Determine whether milestones are appropriate for a given Award
• Monitor study progress; as with any award, continuation, even during the period recommended for support, is contingent upon satisfactory progress. Progress will be monitored by NCATS, using milestones if appropriate for the project. The schedule for these interim reviews will be based upon the duration of the Award. Continuation of funding will be dependent upon the awardee’s ability to show adequate progress.

Areas of Joint Responsibility include:

For those projects where milestones are appropriate, e.g. clinical studies, such milestones will be negotiated between NCATS Program Official and the PD/PI. .

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.

A final progress report, 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.

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)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 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

Philip J. Brooks, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-443-0513
Email: [email protected]

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

Leslie Le
National Center for Advancing Translational Science (NCATS)
Telephone: 301-435-0856
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 74 and 92.