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

The purpose of this FOA is to support pre-clinical studies to evaluate a therapeutic/indication pair for drug repurposing. The repurposing hypothesis should be generated using a developed method that is publicly available. Examples include independent crowdsourcing strategies [e.g., http://www.ncats.nih.gov/ntu/assets/current, http://openinnovation.astrazeneca.com/, or any website that lists experimental therapies (drugs or biologics)], or use of computational algorithms. Supported projects will demonstrate usefulness of the method to improve data usability for future repurposing studies. The initial UG3 award will support the execution of rigorous, pre-clinical target engagement and/or efficacy studies.

Once UG3 pre-clinical milestones have been met, the UH3 award may be made to support clinical trial planning. The purpose of the clinical trial planning phase is to allow time and support for the complete planning, design, and preparation of all the documents necessary to enhance the probability of being able to achieve enrollment goals and determine a definitive outcome for Phase I and Phase II clinical trials for a new therapeutic use. It is intended that results obtained from this FOA could lead to subsequent investigator initiated clinical trials. It is expected that all assets investigated will have started a Phase I trial by the time an award is made. This initiative will support a planning period for a new hypothesis-driven and milestone-defined Phase I (if necessary) and/or planning for a Phase II clinical trial for a new therapeutic use.

Discoveries that clarify the molecular basis of disease provide unprecedented opportunities to translate research findings into new medicines. However, developing a new medicine takes an enormous amount of time, money and effort, mainly due to bottlenecks in the therapeutic development process. Delays and barriers mean that translation of a promising experimental therapy into an approved drug often takes a decade or more. NCATS intends to support strategies that reduce delays, decrease costs and improve success rates.

Drug repurposing/repositioning is one such strategy. Many existing experimental drugs, FDA approved drugs, and biologics already have been tested in humans, and detailed information is available about their pharmacology, formulation, and potential toxicity. By building upon previous research and development efforts, new uses for existing drugs or biologics can be advanced to testing in clinical trials more quickly than starting from scratch. If a new therapy receives regulatory approval, it can be efficiently integrated into clinical practice.

NCATS' approach is generally disease agnostic and does not favor applications in any disease area over another. It focuses not on specific diseases, but what is common among them and the translational science process. NCATS mission is focused on process improvements (new technologies/approaches to accelerate the process of getting more treatments to patients) by developing and deploying solutions that can be used by all translational science researchers. NCATS complements other NIH ICs that also support translational research in disease specific areas.

NCATS is interested in pre-clinical studies that demonstrate utility of an approach for identifying new therapeutic/indication pairs. The strategy should be applicable to other diseases, so that successful use of the method can improve the efficiency of predicting new indications for existing therapeutics.

For pre-clinical studies that meet milestones and go/no-go criteria, NCATS is interested in working with investigators to ensure that clinical trial plans are adequately resourced and properly budgeted before applications are submitted for Phase I and Phase II clinical trials for a new therapeutic use.

This initiative will support studies that test the pre-clinical efficacy of an existing therapeutic for a new indication (therapeutic/indication pair), as identified with a published and/or publicly available computational algorithm, or published and/or publicly available independent crowdsourcing strategy.

For this FOA NCATS will use the following definitions:

• Crowdsourcing: Crowdsourcing occurs when an investigational drug is publicly posted for investigators to propose ideas for new therapeutic uses. Generally, crowdsourcing is an approach used for investigational therapeutics, not therapeutics approved by the FDA, since approved drugs already are known to the public.
• Computational algorithm: A computational algorithm is the business end of bioinformatics. A computational algorithm will mine existing data and, in this case, identify therapeutic/indication pairs for experimental investigation.
• Published or publicly available method: A published method is generally one that is in a peer-reviewed publication. A publicly available method could be available via a website or could be a commercially available product. The publicly available strategy does not need to be free, but it should be available to investigators who would like to use it.

Studies of interest to NCATS include:

• Projects that demonstrate the value of computational algorithms for repurposing due to the potential uptake of successful approaches by the broader research community to subsequently identify additional therapeutic/indication pairs.
• Projects that repurpose a drug or biologic, originally developed or approved for a completely different indication. (For example, a computational prediction that a drug, which was originally developed to treat melanoma and may be effective in treating rheumatoid arthritis, would be of greater interest than if that same drug was predicted to be effective in a different solid tumor cancer).
• Pre-clinical studies that demonstrate the utility of an already published or publicly available method (computational strategy/independent crowdsourcing) for identifying a novel therapeutic/indication pair.
• Projects testing a drug or biologic combination therapy that meets the other requirements of this initiative. Awards made under this FOA can only be used for proof of concept testing and not all required preclinical testing to ascertain toxicity as a combination therapy.

Pre-clinical funds (UG3) may support some or all the following:

• Pre-clinical studies that are a use case for testing an automated strategy for identifying the new therapeutic/indication pair.
• Testing multiple therapies, working through the same mechanism of action or pathway, to identify the therapy with the greatest efficacy.
• Experiments with clear go/no-go decisions that will provide data needed to determine if a subsequent clinical trial planning period is needed.
• Studies that might include testing efficacy of a drug or biologic in an animal model; testing in a physiologically disease-relevant ex vivo human system, when disease-relevant animal models do not exist; or conducting studies to verify target engagement in a model system. However, because investigational therapies explored under this FOA will already have been through a Phase l clinical trial for a different indication, it is expected that IND-enabling pre-clinical toxicity will already be complete.

Clinical trial planning funds (UH3) cover time and support to complete all clinical trial planning activities, including but not limited to:

• Establish the clinical research team.
• Develop clearly defined clinical research hypotheses and outcome measures.
• Assess potential trial design strategies to capture the optimal intervention, dose, and target population.
• Identify inclusion and exclusion criteria.
• Obtain appropriate letters of support, including any letters necessary to demonstrate the support of consortium/site participants, cores, laboratories, pharmacies and other collaborators, including cost-sharing by NIH resources, in the case of intramural collaborators.
• Prepare the following documents during the UH3 award period in preparation for potential future clinical trials:
• Statistical analysis plan.
• Recruitment and retention plan. Model the feasibility of an outcome or intervention in the field. Estimate available populations, attrition rate, or response rate. Determine if adequate adherence to treatment is achievable.
• Develop a plan to address potential delays, and alternatives for conducting the study in the face of adverse outcomes or problems. In addition, this plan should inform the likelihood of accomplishing the trial in the time proposed for a subsequent application for funding of the Phase I and Phase II clinical trial.
• Develop informed consent(s), and/or assent (if applicable).
• Develop a manual of operations with quality control/assurance procedures.
• Write the clinical trial protocol, including a data management plan, data safety and monitoring plan and a plan for collecting adverse events and reporting these events to regulatory authorities and NIH.
• Identify collaborators, enrollment sites, and clinical site(s), which may include negotiating sub-contracts.
• Adaptations and tests of existing survey instruments or protocols for a new population.
• Prepare a data sharing plan.
• If warranted, request a pre-IND meeting to obtain guidance for designing the clinical trial and obtaining approval of the IND. The NCATS program official should be copied on any communication with FDA, if an application for clinical trial support from NCATS is anticipated.
• Prepare FDA and regulatory documents for an IND package submission.
• Obtain Office of Human Research Protection (OHRP) assurances (if not already in place), and initiate IRB approval using a single IRB.
• Develop a detailed project timeline and appropriately resourced budget for conducting and completing the clinical trial, including funding for orderly close-out of clinical sites, and preparation of a final study report.
• Budget plan for site assessment and protocol training that are required prior to initiation of a clinical trial.

NCATS strongly encourages applicants to involve patients or their representatives in the planning of the trial, as appropriate. For example, patient groups could be asked to help review screening instruments, develop clinical trial endpoints that are meaningful to patients, review inclusion/exclusion criteria for feasibility.

Projects that can be rapidly translated to the clinic (pharmacokinetics, pharmacodynamics, safety, and toxicology data are already available) are the priority for funding. Proposed projects are expected to use drugs or biologics that will have started a Phase I clinical trial for another indication by the time an award is made. Most of the IND enabling work will already be complete by the time a new therapeutic use trial begins. The following types of projects are not expected to improve the efficiency of accelerating new therapies to patients and are not a high priority for funding.

• Projects that require reformulation: Funding will not be provided for reformulation. The only exception is for pediatric indications, which may need to be formulated as a solution/suspension for oral administration (ages 6 to 11) or a small tablet/capsule (ages 12 to 18). Palatability issues may also have to be addressed for pediatric administration.
• Projects that require a changed route of administration: these studies are not anticipated to be able to enter clinical testing rapidly without added pre-clinical pharmacology/toxicology experiments (more time/expense).

The following will not be considered for support under this FOA:

• Applications that propose repurposing projects that are solely the result of traditional experimental methods.
• Applications for drug development that are the next logical step in an existing project.
• Projects that are the result of a standard literature search or database search with no improved efficiency.
• Projects that follow a previously demonstrated pathway.
• Projects that are not truly a new use of an existing therapy (e.g., clinicaltrials.gov lists other trials for the therapeutic/indication).
• Repurposing ideas that result solely from physically screening a library of drugs to identify the therapeutic/indication pair.

The following will not be funded during any phase of awards made under this FOA:

Projects that meet the NIH definition of a clinical trial, projects that propose testing the effectiveness of a dietary supplement, projects designed to pilot test ideas in human subjects, or projects that involve subject screening/recruitment will not be funded during any phase of awards (UG3 or UH3) made under this FOA.

Applicants must plan for both a UG3 and UH3 phase in their application. The UG3 phase must include milestone-driven pre-clinical work to determine if a clinical trial planning period is justified. Projects should have clear, testable hypotheses and the research plan should use quantifiable measures for making a go/no-go decision to progress to clinical trials. These studies might include testing efficacy of a drug or biologic in an animal model; testing in a physiologically disease-relevant ex vivo human system, when disease-relevant animal models do not exist; or conducting studies to verify target engagement in a model system.

Funding of the UG3 phase does not guarantee funds for the support of the clinical trial planning phase (UH3 phase). Funding of the UH3 award will be determined by successful completion of UG3 scientific milestones as determined by the NIH.

It is expected that elements completed during the clinical trial planning will be incorporated into a subsequent application for support of Phase I and Phase II clinical trials for a new therapeutic use.

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 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.

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, 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.

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

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

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

The letter of intent should be sent to:

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

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.

Other attachments:

I. Study Agent Summary Table Description (limited to 2 pages)

Attach a table for the drug or biologic selected for use in the project that contains the following information (when available).

• Name of therapeutic.
• Mechanism of Action (when available).
• Original Development Indication(s).
• List the new Indication without repeating the description provided in Research Strategy.
• List the method used to identify new therapeutic use [independent crowdsourcing or computational algorithm (summarize), without repeating the description provided in Research Strategy.

II. Resource Access Plan

Attach a Resources Access Plan with the following information:

• Indicate if the active pharmaceutical ingredient is available for purchase, or otherwise available at the applicant institution. If access to an active pharmaceutical ingredient is pending, a letter of support should be separately provided from the asset provider. Generally, an MTA should provide sufficient assurance of timely access to the pre-clinical material.
• The Resource Access Plan should address any additional complexities associated with materials and data obtained from foreign sources, if applicable.
• Documentation that the investigators have access to or a plan to gain and maintain access to proprietary information (when applicable), assays, reagents, models, technology, data and all that is necessary to execute the proposed experiments.
• For projects that propose using an asset owned by a small company, the applicant must explain how risks will be mitigated for federal investment. Include a plan to access the preclinical material needed during the proposed project period, if an NIH award is made.
• In order to help ensure rapid transition to future clinical trials, the new therapy must have at least started Phase I clinical testing in humans for another indication by the time an award is made under this initiative.
• Include an explanation that a Phase l trial of the drug or biologic has been conducted (publication, clinicaltrials.gov registration number, etc.) or is underway for another indication; or include documentation from the asset provider that clearly states that:
• a Phase I trial has been completed for a different indication; or
• a Phase I trial will be initiated for a different indication by the time an award is made.

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: Applicants must provide a single Specific Aims attachment that describes the aims of both the UG3 and UH3 phase of the project. All applications must include a clinical trial planning phase (UH3).

Research Strategy:

UG3

• Include an overall plan to assess the validity of the biological hypothesis for use of the drug or biologic for the new indication, so that the rationale for a clinical trial will be evident if preclinical studies demonstrate efficacy.
• Without repeating information submitted elsewhere, briefly describe the patient population and unmet medical need that would be addressed if the proposed research successfully translates to the clinic in later stages of development.
• Explain how the project will improve the success or efficiency of translating pre-clinical studies into clinical testing.
• Describe the uniqueness of the therapeutic/indication pair that will be investigated in this project.
• Describe the novelty of this target class for the proposed indication or how the mechanism of action of the therapeutic has been understudied for the indication.
• Include a description of Milestones for the UG3 phase. The UG3 Milestones should be specific, measurable, and scientifically justified. The intent of the pre-clinical studies is to provide data that would determine whether a clinical trial is justified and that an UH3 award to support clinical trial planning is warranted. The experimental results should provide proof of concept in a compelling go/no go manner for proceeding to clinical trial planning followed by a subsequent application for a clinical trial. Applicants should describe how they will achieve unbiased results, when describing the experimental design of proposed studies.
• Include a timeline for assessing milestone progress in the UG3 stage, and when a determination to proceed to the UH3 will be made, within context of the milestones.

Although clinical trials will not be supported under this FOA, to help ensure rapid transition to future clinical trials, the therapeutic must have at least started Phase I clinical testing in humans for a different indication by the time an award is made under this initiative.

UH3

The trial planning period is intended for time and financial support to develop clinical trial documents and to fully design a clinical trial for projects that meet pre-clinical milestones. Applications must include the following:

• A description of how the planning period will be used and descriptions and timing of the activities to be carried out during the planning period, including participants in the planning process and their roles;
• Information about how the clinical trial documents will be developed; and a description of how the trial will be organized and managed, including the plans to identify and select additional collaborators, if applicable.
• Anticipated need for a trial, potential impact of the results of the trial, and how the trial will test overall hypothesis(es) proposed;

Letters of Support: The applicant organization must obtain a letter of support from the manufacturer, stating that they will provide the active pharmaceutical ingredient to be tested in the pre-clinical studies, if it is not commercially available or already available at the applicant organization. Generally, an MTA should provide sufficient assurance of timely access to the pre-clinical material.

Letters of support should include acknowledgement of testing multiple drugs or biologics, if applicable, and the timeframe for expected delivery of compounds to be used.

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.

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.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

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.

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.

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

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the 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 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?

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

Specific to this FOA: How novel is the therapeutic/indication pair?

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

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

Specific to this FOA: Is there evidence that the drug/biologic would be ready to be used in clinical studies if suitable data are obtained from the pre-clinical work? Are there clear, testable hypotheses? Are there quantifiable measures for making go/no-go decisions?

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?

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.

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.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

• Determining the experimental research approaches, designing protocols, drafting project milestones and go/no go decision points, and conducting the project within the guidelines of the FOA.
• Submitting a Milestone Report, included in the Research Performance Progress Report (RPPR).
• Retaining custody of and having 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 have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The Program Collaborator will be responsible for the normal scientific and programmatic stewardship of the award.
• The Program Collaborator will monitor performance through review of annual reports and monitor compliance with NIH procedures.
• The Program Collaborator will approve modifications to the research plan, based on emerging data and/or other issues that impact progress of the project.
• The Program Collaborator will determine if the awardee has met/achieved milestones throughout the UG3 and/or UH3 stages of the project.
• NCATS reserves the right to obtain periodic external review and recommend reviewers for an assessment of progress and achievement of milestones.
• NCATS reserves the right to terminate or curtail a UG3 or UH3 project for any of the following reasons: (1) inadequate progress in meeting the pre-negotiated milestones and timelines; (2) failure to meet the go/no go milestone(s) for transition from the UG3 to UH3; and/or (3) failure to comply with the Terms and Conditions of Award

Areas of Joint Responsibilities include:

Participate in meetings to discuss progress, obstacles and any other related issues and/or activities. The milestones and timelines proposed by the PD(s)/PI(s) may require revision and renegotiation by NCATS Program Official during the project period. The PD(s)/PI(s) and NCATS must agree on all such revisions.

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 member chosen by the individual awardee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. 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. Follow 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.

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

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

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

Bobbie Ann Mount, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0824
Email: [email protected]

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

Erin Davis
National Center for Advancing Translational Research (NCATS)
Telephone: 301-451-4238
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.