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 clinical trial planning for studies that will 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., https://ncats.nih.gov/ntu/assets/current, https://openinnovation.astrazeneca.com/, or any website that lists experimental therapies (drugs or biologics)], or use of computational algorithms.

The clinical trial planning phase is to allow time and support for the complete planning, design, and preparation of all the documents and development of other essential elements 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 implementation of clinical trials. It is expected that all assets investigated will have completed a Phase I trial by the time an award is made under this FOA. 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. Funds provided by NCATS may only be used to support planning of phase III clinical trial activities, but not the phase III trial itself except in the case of a rare disease or condition that meets certain criteria.

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 licensed 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.

The intent is for NCATS to work with investigators to ensure that clinical trials are adequately resourced and properly budgeted before applications that request support for implementation of clinical trials are submitted for Phase I and Phase II clinical trials for a new therapeutic use.

This FOA intends to support clinical trial planning for innovative ideas for the discovery of new therapeutic uses of existing drugs/biologics in previously unexplored diseases. The project may plan clinical trials for the use of an existing marketed or investigational drug or biologic as: 1) a stand-alone intervention; or 2) an adjunctive intervention with existing standard of care (if there is no evidence of drug-drug interactions with the proposed standard of care treatment). In either case, this initiative will support clinical trial planning on a therapeutic/indication pair, which was identified with a published or publicly available computational algorithm, or publicly available independent crowdsourcing strategy to identify a new therapeutic/indication. The method should already be published or publicly available, so it can be disseminated to improve data usability for future repurposing studies.

Phase II clinical trials may be planned for a common disease. If needed, Phase I clinical trials may also be planned for the new indication for a common disease. Rare disease trial plans should follow Draft FDA Guidance: Rare Diseases: Common Issues in Drug Development Guidance for Industry . Specifically, one or more adequate and well-controlled clinical trial(s) may be planned in a rare disease population.

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 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 a commercially available product. The publicly available strategy does not need to be free, but it should be available to investigators that would like to use it.
• Phase I clinical studies are planned for the target patient population to evaluate safety, determine a safe dose range, and identify side effects prior to conducting a Phase II clinical trial.
• Phase II clinical trials are planned for a larger patient population, typically 150 subjects or less for trials in adults. The purpose of the Phase II clinical study is to eventually test for a preliminary signal of efficacy.
• Rare Disease: A disease or condition that affects fewer than 200,000 people in the U.S.
• Common Disease: Any disease or condition that is not a rare disease.
• Clinical trials for Rare Disease: Due to small numbers of available patients, the terms Phase I, II and III clinical trials may not always be appropriate. Therefore, well-controlled studies in a rare disease population may be planned to demonstrate substantial evidence of efficacy in treating or preventing the condition and to establish evidence of safety for that use. Evidence of efficacy for a rare disease may be established in one or more adequate and well-controlled clinical trials in the identified population. See Rare Disease: Common Issues in Drug Development Guidance for Industry for more information: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM458485.pdf

Planned clinical trials should use the selected therapeutic in its existing formulation/route of administration. The only exception is for pediatric indications, which may need to be formulated for a pediatric population. Examples include formulation as a solution/suspension for oral administration (ages 6 to 11) or a small tablet/capsule (ages 12 to 18). Palatability issues also may have to be addressed for pediatric administration.

Organizations involved in the research project should be identified at the time of application. To help ensure rapid transition to future Phase II clinical trials, the therapeutic must have completed Phase I clinical testing in humans for a different indication by the time a clinical trial planning award is made.

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, and/or review inclusion/exclusion criteria for feasibility.

Clinical trial planning funds cover time and support to complete all clinical trial planning activities, including, but not limited to all elements that enable the applicant to develop a complete application for subsequent implementation of a Phase I and/ or Phase II clinical trial for the new therapeutic use, or a rare disease clinical trial for a new therapeutic use:

• 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.
• Collect small but statistically meaningful feasibility data that can be extrapolated to a larger population. This may be used to determine how fast or slow enrollment will occur, to identify appropriate inclusion and exclusion criteria, and to determine feasibility for the enrollment goals to be achieved at the geographical sites represented. Studies such as evaluations of databases, interviews, surveys, and focus groups are allowable. These studies should be well designed and rigorous so that they answer the questions of whether a population of sufficient size can be identified and whether that population would have interest in participating in the study.
• 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.
• During the clinical trial planning period, the applicant will plan to demonstrate the capacity to obtain access to the drug product in the dosage form that will be administered to patients, if a subsequent clinical trial is conducted. The drug product must meet critical quality attributes for pharmaceutical development. Learn more: https://www.fda.gov/downloads/drugs/guidances/ucm073507.pdf
• Availability of the Investigational Product and Investigational New Drug status (Required): Obtain documentation of access to the selected therapeutic that is manufactured according to U.S. Food and Drug Administration chemistry, manufacturing, and controls standards and Good Manufacturing Practices, and access to any data (e.g., Investigator's Brochure, study reports, ability to cross reference the Drug Master File) needed for obtaining regulatory approval, and for conducting the proposed clinical trials. A letter of support from a pharmaceutical partner, who will provide drug, may be provided with a contingency that the drug will be provided (pending NIH funding).
• Regulatory status: 1) Indicate whether an FDA-approved therapeutic is available for purchase; 2) whether a new IND is not needed as documented through communication with FDA; 3) for studies where asset is provided by a pharmaceutical partner a letter should be provided indicating that a Collaborative Research Agreement or equivalent will be executed, and the PD/PI has the right to cross-reference specific sections of the pharmaceutical company partner's IND/Drug Master File, etc.
• A Resource Access Plan for obtaining the drug product should address any additional complexities associated with materials and data obtained from foreign sources, if applicable.
• If the drug or biologic to be tested is not marketed, and evidence that a Phase I trial for a different indication has been conducted on the drug or biologic (publication, clinicaltrials.gov registration number, etc.) is not available, include documentation from the therapeutic provider that clearly states that a Phase I trial for a different indication has been completed and indicates by whom the trial was conducted.
• Prepare the following documents 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).
• 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.
• Develop a manual of operations with quality control/assurance procedures. A data quality management plan should be developed for all sites to ensure the quality of the data collected.
• Identify collaborators, enrollment sites, and clinical site(s), which may include negotiating sub-contracts.
• Adapt and test existing survey instruments or protocols for a new population. For example, determine if the enrollment goals can be achieved, determine if the patients are interested in the therapy, and determine if patients would be interested in participating in the protocol.
• Prepare a data sharing plan, as appropriate and consistent with achieving the goals of the program 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.
• Develop a budget for site assessment and protocol training.
• Plan for centralized site monitoring (when appropriate) if multiple sites are involved. Learn more: https://www.fda.gov/downloads/Drugs/Guidances/UCM269919.pdf
• Develop a plan to access the new therapy, so that a resource access plan for the applicant may demonstrate capacity to access drug product

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

• Projects that meet the NIH definition of a clinical trial,
• Projects that involve prospective enrollment of patients, are designed to administer therapies to human subjects, or are designed to randomize human subjects.
• Projects that propose to obtain efficacy measures in human subjects, or
• Projects that involve subject recruitment (other than focus groups, interview, or surveys) for a clinical trial will not be funded under this FOA.
• Projects designed to validate patient reported outcomes in survey instruments.
• Support for pre-clinical studies.
• Applications that propose clinical trial planning for projects that are solely the result of traditional experimental methods.
• Applications for support of clinical trial planning for drug development projects 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 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.
• Applications that propose planning a clinical trial for a drug or biologic that has not completed a Phase I clinical trial for a different indication.
• Applications that propose to plan a clinical trial for a formulation of a drug/biologic that is different from what has been tested in phase I studies previously. The only exception is for pediatric indications, which may need to be formulated for administration in a pediatric population.
• Projects that plan to test the efficacy of a dietary supplement alone or in combination with other treatments.
• Applications that plan phase III clinical trial activities for a common disease or condition.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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, 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: Lambert@mail.nih.gov

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 Asset 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).
• State the new Indication without repeating the description provided in Research Strategy.
• State the method used to identify new therapeutic use [independent crowdsourcing or computational algorithm (summarize), without repeating the description provided in Research Strategy.

II. Feasibility of obtaining the drug product, necessary data, and paperwork for regulatory approval.

While a complete plan for obtaining the drug product will be developed during the clinical trial planning period, applicants need to have considered whether the proposed drug product, necessary data and documents for regulatory filings are feasible to obtain for subsequent clinical trials.

• To help ensure rapid transition to future clinical trials, the new therapy must have completed Phase I clinical testing in humans for another indication by the time an award is made under this initiative.
• Indicate whether an FDA-approved therapeutic drug product is available for purchase.
• Indicate whether a new IND is likely to be needed, and whether it is feasible to access or cross reference any data needed for regulatory approval.
• If the therapy is experimental, will a pharmaceutical partner consider providing the drug to an investigator for clinical trials on the new indication?
• If a letter stating that a pharmaceutical partner may consider providing access to drug product is not available, is it feasible to access the data and information needed to have the drug product manufactured according to critical quality attributes for pharmaceutical development. Learn more: https://www.fda.gov/downloads/drugs/guidances/ucm073507.pdf

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 Aimsattachment that describes the aims of proposed clinical trial planning period (not aims for the actual clinical trial).

• 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.

Research Strategy:

The trial planning period is intended for time and financial support to collect feasibility data, to develop clinical trial documents, and to fully design a clinical trial. Applications must include background on the following:

• Describe the need for the clinical trial that is being planned;
• Discuss the potential impact of the results of the trial that is being planned;
• Give a brief description of the study population characteristics; and
• Provide an overview of how the trial will test the overall hypothesis(es) that will be tested.

The Research Strategy must also include: Plans for collecting feasibility data. This data collection should use existing datasets and resources (e.g. databases), whenever possible. Depending on the project, it may be helpful to assess feasibility using patient samples (e.g., estimate prevalence of a genotype that affects drug metabolism). In addition, demonstration of an appropriate and interested patient population may be demonstrated by interviews, surveys, focus groups or prior performance at the site. The feasibility data collection will provide the following types of information:

• Availability of individuals with the disease or condition being tested at the study site. Whether the distribution by age, sex/gender, race, and ethnicity is representative for the disease/condition being tested;
• Feasibility of inclusion/exclusion criteria;
• Based on existing literature and data, determine if drug-drug interactions exclude too many subjects with the condition for the experimental therapy to be feasible to use in the proposed study population;
• Estimate how many study sites will be needed to complete the study within a reasonable timeframe. For applications that will request funds from NCATS for subsequent clinical trials, the reference timeframe is one year for a Phase I clinical trial, two years for a Phase II clinical trial, three years for an adaptive designed clinical trial; or up to three years to demonstrate substantial evidence of efficacy in treating or preventing a rare disease or condition and to establish evidence of safety for that use in a rare or neglected disease population;
• 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; and
• 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.

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:

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

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

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

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. Any instructions provided here are in addition to the instructions 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?

Specific to this FOA: Does the team have adequate expertise in clinical trial policy and regulatory experience to prepare the clinical trial documents?

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?

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 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 as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• All aspects of the planning award.
• Developing and adhering to the pre-determined timeline for planning activities.
• Accepting close coordination, cooperation, and participation of NCATS staff in scientific and technical management of the planning award.
• Planning and participating in quarterly update meetings with NCATS staff.

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

The NIH Project Scientist will be responsible for:

• Reviewing and providing feedback on the data and all documents prepared during the award period.
• Reviewing and commenting on critical stages of the overall study planning progress based on the established timeline.
• Implementing adjustments to the study planning timeline as needed.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Participating in scheduled teleconferences with awardees.

Dispute Resolution:

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

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

A final 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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (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: newtherapeuticuses@mail.nih.gov

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email: Lambert@mail.nih.gov

Leslie Le
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0856
Email: leleslie@mail.nih.gov

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.