It is critical that applicants follow the Research (R) 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

Purpose

The Clinical and Translational Science Award (CTSA) Program Collaborative Innovation Award (CCIA) supports collaborative research activities that develop innovative solutions that will improve the efficiency, quality and impact of turning laboratory, clinic and community observations into interventions that improve the health of individuals and the public. This funding opportunity announcement (FOA) will support investigators from two or more CTSA Program hub institutions (see below under Eligible Individuals) to either: 1) form new collaborations, or to 2) significantly expand the scientific scope of existing collaborations, or to 3) engage new collaborators in pre-existing collaborations to solve a translational science problem no one hub can solve alone, or disseminate a solution to a translational science problem developed at one hub to other hubs, in so doing testing its robustness to different hub environments and structures and adapting it for further dissemination outside the CTSA Program consortium if appropriate.

Background

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. Under NCATS leadership, the CTSA Program supports a national consortium of medical research institutions called hubs ? that work together to improve the translational research process to get more treatments to more patients more quickly. The hubs collaborate locally, regionally, and nationally to catalyze innovation in training, research tools and processes.

The overall purpose of the CTSA program is to deliver scientific and systems change that solve the many outstanding problems limiting the efficiency, effectiveness, and reach of clinical translational research, and thus get more treatments to more patients more quickly across the country. To do that, the program focuses on widely appreciated systematic barriers including (exemplary only; not intended to be exhaustive or exclusive):

• Data interoperability
• Biomarker qualification process
• Regulatory science
• Clinical trial networks
• Patient recruitment
• Electronic Health Records for research
• Harmonized IRBs
• Clinical diagnostic criteria
• Clinical outcome criteria (e.g., PROs)
• Adaptive clinical trial designs
• Shortening time of intervention adoption
• Methods to better measure impact on health (or lack thereof)
• Data transparency/release
• Integration of project management
• Incentives/credit for team science
• Incentives/credit for health improvements
• Education/Training (scientific and cultural)
• Collaborative structures

Innovations in these and related areas will be catalytic to translational efficiency and the development and delivery of interventions that improve the health of individuals and communities. It is not expected that every hub should have the expertise or capability to address all of these issues, but the aggregate program can and should. Beyond these strategic focus areas, this FOA defines domains of activity for the CTSA Program hubs that are intended to advance progress in these areas broadly, as well as a set of standards and resources that should be available at each hub to allow it to serve as a leading center for translational innovation and facilitate collaboration among the hubs. The academic health centers that make up the CTSA Program are referred to as hubs to indicate their central role in their local environments where they coordinate and collaborate with multiple spokes such as affiliated hospitals, clinics, and community health centers. 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, and on a national level.

Translation is defined by NCATS as 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. Translational research is defined by NCATS as the endeavor to traverse a particular step of the translational process for a particular target or disease. Translational science is the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Translational research focuses on the specific case of a target or disease, whereas translational science is focused on the general case that applies to any target or disease. Its focus areas are the common causes of inefficiency and failure in translational research projects (for example, incorrect predictions of the toxicity or efficacy of new drugs, lack of data interoperability and ineffective clinical trial recruitment). As these causes are the same across targets, diseases and therapeutic areas, advances in translational science will increase the efficiency and effectiveness of translational research in all therapeutic areas. Like any other science, translational science seeks to elucidate general operative principles in order to transform translation from an empirical, phenomenological process into a predictive science.

Every stage of the translational process, from target validation through intervention development to public health benefit assessment, is currently fraught with inefficiency and in need of bold, new, innovative solutions. Thus, there is a corresponding need for bold, new, innovative 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.

Individual CTSA Program hubs, and 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 Program hubs, and their multiplicity nationwide, suggests that fostering cross-CTSA Program innovation development and implementation could transform the nation's translational effectiveness in unprecedented ways. This FOA therefore seeks to encourage all CTSA Program 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.

Specific Objectives

This FOA aims to support applications for innovative collaborative investigations (involving two or more CTSA Program hubs) into improvements of the methods of translational research, at any part of the translational science spectrum. It is anticipated that the complementary efforts of two or more CTSA Program hubs in collaborative projects will substantially enhance the effectiveness of the CTSA Program in solving high priority translational research problems. This FOA therefore aims to support innovative and collaborative experimental translational science research projects carried out in the CTSA Program that are characteristic of the R21 activity code.

The R21 activity code is intended to encourage new exploratory and developmental research projects. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on translational science.

In view of these considerations, this FOA will enable collaborative teams of investigators, from at least two different CTSA Program hub institutions, to explore novel, generalizable approaches to important translational science questions, and to assess the utility and feasibility of such approaches. Collaborations that bring together ideas, theories, methods and approaches from disparate scientific disciplines are particularly encouraged.

Projects funded with these awards should:

• Use experimental approaches targeted at overcoming specific, current translational science challenges and barriers;
• Be clearly generalizable beyond the specific example or use case addressed in the application;
• Have outcomes that are clearly defined and measurable and that support clear decisions (go/no-go) with regards to next steps;
• Build on program successes and reinforce areas of progress; and
• Where appropriate, include partners in addition to academic investigators (e.g. industry, patient advocates, community members, citizen scientists).

Examples of projects that would be supported under this program include, but are not limited to:

• Novel translational collaborations with the Precision Medicine Initiative
• Translational studies of the human microbiome
• Collaborative in silico drug screening efforts
• Novel approaches to implementation science
• Innovative utilization of wearable/mobile devices for translational science
• Evaluating different methods of engaging communities in research, including recruiting individuals from understudied populations into clinical or translational research studies
• The use of telemedicine approaches in rare disease research
• Adapting technology and methodology shown to be successful in other domains to address challenges in clinical and translational research
• Innovative approaches to translational science education and training
• Innovative clinical trial designs
• Innovative informatics and IT solutions to translational science problems
• Innovative approaches to the collection and utilization of direct patient reported outcomes
• Novel strategies for working with other health care agencies [e.g. the Health Resources and Services Administration (HRSA), the Centers for Medicare & Medicaid Services (CMS)]
• Pilot studies of clinical trials of drugs targeting shared molecular etiologies underlying multiple diseases, for diseases other than cancer
• Innovative translational science approaches to addressing the ongoing opioid epidemic

Examples of projects that would not be supported under this FOA include, but are not limited to:

• Direct dissemination of an approach, tool, or methodology that has already been developed at one CTSA Program hub to one or more CTSA Program hubs
• Incremental improvement or enhancement of an established approach
• Continuation of an ongoing collaborative translational project, even if it involves investigators from different CTSA Program hubs
• Translational research projects focused on a specific disease that does not have broader implications for translational science

In general, the goals of this R21 program are similar to those of the CCIA U01 opportunity (PAR-19-099). The main difference is that, to a greater extent than the CCIA U01 opportunity, this FOA encourages highly innovative, exploratory projects that can be completed within a two-year time frame, with the recognition that such projects may involve a greater risk of failure rate. To mitigate this risk, the duration and scope of these projects are significantly less than for the CCIA U01 opportunity. The requirement for inclusion of a clear definition of success/failure, as well as a plan for dissemination of the results, is intended to ensure that the collective translational science knowledge base will be expanded by all projects supported by this R21 program.

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.

• An application must involve investigators who are supported by CTSA Program hub institutions from at least two different and currently funded CTSA Program hubs as of the due date of the application. A CTSA Program hub is defined as a UL1 award with a linked KL2 award and an optional TL1 award. A hub that is in no-cost extension (NCE) status is not considered a currently funded CTSA Program hub (see https://ncats.nih.gov/ctsa/about/hubs). CTSA Program hub institutions include the recipients of the CTSA Program hub award, as well as any institutions listed as partners in the CTSA Program hub UL1 awards.

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) 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.

The PD/PI or contact PD/PI must be employed by and/or recipient of funding from a currently funded CTSA Program hub institution as defined above in Eligible Organizations. Investigators who are not employed by and/or a recipient of funding from a CTSA Program hub institution but who wish to bring an innovative project to the CTSA Program, can co-direct a project in partnership with a contact PD/PI who is employed by a currently funded CTSA Program hub institution using the multiple PD/PI option.

See required Letters of Support.

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).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, 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.

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: 301-480-3660
Email: [email protected]

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 research question or the critical gap in translational science being addressed, and its significance. As applicable to the specific project, applicants should describe the potential transformative effect that the research will have on some domain of translational science. 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. Include a statement of how, if successful, the specific translational science research problem, that focuses on the specific case of a target or disease, can be generalizable to other targets or diseases.

Provide a description of and rationale for the proposed innovation. Describe, if successful, how would the proposed innovation transform some domain of translational science? The description 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. 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.

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: Describe how the project will build on the existing strength of the CTSA Program and involve investigators from two or more CTSA Program hub institutions to either: 1) form new collaborations, or to 2) significantly expand the scientific scope of existing collaborations, or to 3) engage new collaborators in pre-existing collaborations to address the purpose of this FOA. State whether the collaboration is new, expanding the scientific scope of an existing collaboration, or is engaging new collaborators in pre-existing collaborations to address the translational science challenge. Describe the plans and timeframe for how multiple CTSA Program hubs will participate in this research, identifying those responsible for various efforts, declared milestones, metrics, individual responsibilities, timelines and plans for dissemination of research results throughout the CTSA Program.

Describe any additional collaborative effort that will contribute to the project, such as other clinical sites, those with patient organizations, or partners in the private sector in the area of diagnostics, therapeutics or preventive measures. If applicable, 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: Identify any perceived clinical or scientific barriers or ethical issues and solutions proposed. Describe potential contingency plans and alternative approaches to completing the aims of the project.

Defining success: Define success for the proposed project, describe how success can be evaluated and measured, define outcomes that result in a go/no go decision regarding the feasibility of the proposed approach, provide a timeline for milestones of the project, and describe how they plan to disseminate their successes across the CTSA Program and potentially beyond.

Describe what the unique features of the scientific environment, subject populations, or collaborative arrangements will make this project successful. Describe whether the project builds on an existing discovery or development and whether, if successful, it has the potential to effect translational research. Describe whether the existing strengths and resources of the CTSA Program, the individual hubs and/or collaborators will be leveraged to complete the stated aims

For projects that involve clinical research, describe how Institutional Review Board (IRB) approval and monitoring will be streamlined, e.g. by the use of a single IRB or IRB of record.

For this particular announcement, note the following:

This R21 exploratory/developmental grant supports exploratory investigations of novel scientific approaches, tools, or technologies that have the potential for significant impact on translational science. An R21 grant application need not have extensive background material or preliminary information.

Letters of Support: Each collaborating investigator is required to include a letter of support from the PD/PI of the CTSA Program hub with which they are associated. For multiple investigators from the same CTSA Program hub, one letter of support from the CTSA Program hub PD/PI is sufficient. Where relevant, include letters of support or other documentation of partnerships or collaborative efforts 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. Letters of support must detail how the CTSA Program hub(s) will provide support to the project (e.g. resources and assistance in dissemination of the outcomes of the project across the CTSA Program and possibly beyond).

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:

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 (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 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

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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). 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.

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) 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 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.

For this particular announcement, note the following:

This FOA is intended to support highly innovative, exploratory, and collaborative research projects in the CTSA Program, with the goal of assessing utility and feasibility of proposed innovation(s). The supported collaborative research activities will enable the development of innovative solutions that will improve efficiency, quality and impact of the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public. This FOA is intended to support investigators from two or more CTSA Program hub institutions to either: 1) form new collaborations, or to 2) significantly expand the scientific scope of existing collaborations, or to 3) engage new collaborators in pre-existing collaborations to address the purpose of this FOA.

This R21 exploratory/developmental grant supports exploratory investigations of novel scientific approaches, tools, or technologies that have the potential for significant impact on translational science. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance translational science. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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 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).

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 the prior research that serves as the key support for the proposed project rigorous? 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, does it have the potential to have a transformative effect on some aspect of translational science? If the project succeeds, will the approach be generalizable to other targets or diseases?

In addition, for applications involving 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 each of the collaborators make a significant contribution to the overall project? Are the roles and responsibilities of each collaborator clearly identified? If applicable, do the applicants effectively expand the scientific scope of an existing collaboration to address the aims of the project? If applicable, do the applicants effectively engage new collaborators in pre-existing collaborations to address the aims of the project? If applicable, do the new collaborators play a substantial role, and is there evidence of commitment and support from all the prospective collaborators?

In addition, for applications involving 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? Does the project open a new avenue of translational research, or result in a systematic improvement over current approaches? To what extent is the proposed research an extension of ongoing research or a new project for the investigators? Will the results be generalizable to translational research challenges across multiple CTSA Program hubs, as well as the broader translational research community? If the project succeeds, will the proposed innovation transform some domain of translational science?

In addition, for applications involving 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 included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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? Is the collaboration clearly described? Are the timeline and plan to measure the success of the proposed project adequate? Is the plan to disseminate the results of the project throughout the CTSA Program adequate? 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?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed? Is there a description for using a single IRB or IRB of record, and is commitment to this plan demonstrated by letters from all relevant Institutional Officials?

In addition, for applications involving 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? Does the project leverage and build on the existing strengths and resources of the CTSA Program, the individual hubs and/or collaborators?

In addition, for applications involving 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.

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 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 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 individuals of all ages (including children and older adults) 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.

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; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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 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 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. 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.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.

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 https://www.hhs.gov/civil-rights/for-individuals/section-1557/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 https://www.hhs.gov/civil-rights/for-individuals/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

Not Applicable

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 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, application errors and warnings, documenting system problems that threaten on-time submission, and 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)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Soju Chang, M.D., M.P.H.
National Center for Advancing Translational Sciences (NCATS)
Telephone: (301) 827-9206
E-mail: [email protected]

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

Brian Quillin
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0844
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.