Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title
Clinical Trial Readiness for Rare Diseases, Disorders, and Syndromes (R03 Clinical Trial Not Allowed)
Activity Code

R03 Small Grant Program

Announcement Type
Reissue of PAR-18-952
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-22-100
Companion Funding Opportunity
PAR-22-101 , R21 Exploratory/Developmental Grants
Assistance Listing Number(s)
93.350, 93.865
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) invites researchers to submit applications for support of clinical projects that address critical needs for clinical trial readiness in rare diseases. The initiative seeks applications that are intended to facilitate rare diseases research by enabling efficient and effective movement of candidate therapeutics or diagnostics towards clinical trials, and to increase their likelihood of success through development and testing of rigorous biomarkers and clinical outcome assessment measures, or by defining the presentation and course of a rare disease to enable the design of upcoming clinical trials.

Key Dates

Posted Date
February 03, 2022
Open Date (Earliest Submission Date)
May 17, 2022
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
May 17, 2022 May 17, 2022 Not Applicable October 2022 January 2023 April 2023
October 17, 2022 October 17, 2022 Not Applicable January 2023 May 2023 July 2023
May 15, 2023 May 15, 2023 Not Applicable October 2023 January 2024 April 2024
October 17, 2023 October 17, 2023 Not Applicable January 2024 May 2024 July 2024
May 13, 2024 May 13, 2024 Not Applicable October 2024 January 2025 April 2025
October 17, 2024 October 17, 2024 Not Applicable January 2025 May 2025 July 2025

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date
October 18, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in 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 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Attaining effective therapies for rare diseases is challenging due to their low prevalence resulting in fewer patients, clinicians, researchers, and resources compared to common diseases. This leads to gaps in our understanding of a rare disease's natural history, and a dearth of suitable biomarkers or clinical outcome measures, or of other components needed to design, conduct, and interpret rigorous clinical trials.

This Funding Opportunity Announcement (FOA) invites researchers to submit applications for support of clinical projects that address critical needs for clinical trial readiness in rare diseases. The Office of Rare Diseases Research (ORDR) within the National Center for Advancing Translational Sciences (NCATS), along with the Institutes and Centers (ICs) listed in Part I at the National Institutes of Health (NIH), intend to facilitate rare disease research by enabling efficient and effective movement of candidate therapeutics or diagnostics towards clinical trials, and to increase their likelihood of success through development and testing of rigorous biomarkers and clinical outcome assessment measures, or by defining the presentation and course of a rare disease to enable the design of upcoming clinical trials.

Background

The NIH supports translational and clinical research on a broad range of diseases that are defined as rare; that is, diseases affecting fewer than 200,000 individuals in the United States (per the Rare Diseases Act of 2002). Collectively, there are an estimated 7,000 rare diseases, which affect approximately 25-30 million people in the United States. Most are serious or life-threatening, leading to significant morbidity and mortality, and most affect children. Despite advances in our understanding of the causes and mechanisms of many rare diseases, effective treatments are available for fewer than 5%.

To address this significant public health concern, the NIH investment into discovery research has contributed to unprecedented opportunities to translate scientific advances into better treatments. Gene therapy and related approaches are an example of opportunities that have resulted from technological advances. However, to evaluate such potentially transformative treatments, researchers, biopharmaceutical companies, and regulators need high quality, natural history data, as well as biological and clinical outcome measures fit for the intended purpose. The absence of such information often represents a bottleneck in therapy development for many rare diseases.

This initiative aims to support studies that address these gaps in understanding of disease natural history and appropriate outcome measures. Given the large number of rare diseases and the limited funding available, this initiative will focus on studies for which it can be demonstrated that there are clinical development candidates for the indication, and for which there are unmet medical needs. The initiative will promote partnerships among academic investigators, industry, and patient groups, and will encourage interactions with the Food and Drug Administration (FDA). Use of existing data standards, tools, information technology platforms, and candidate clinical outcomes measures and biomarkers will also be encouraged, rather than the discovery or de novo development of such tools and resources.

Definitions

This FOA describes a specialized type of clinical research that is intended to provide data necessary for the design of future clinical trials.

Clinical trial readiness is the state of having validated clinical research tools and knowledge of disease natural history necessary for the design of efficient clinical trials. Validated clinical research tools can include biomarkers or clinical outcome assessment measures that are fit-for-purpose within a defined context of use relevant to the clinical trials. Knowledge of disease natural history necessary for clinical trial design can include characteristics for stratification or determining inclusion and exclusion criteria; the stage of disease progression that may be responsive to treatment; and data needed for determining sample size through power calculations.

This FOA uses terminology defined in the BEST (Biomarkers, EndpointS, and Other Tools) Resource, which was developed by the FDA-NIH Biomarker Working Group. Investigators are encouraged to use the terms below, where appropriate in their applications. Guidance to reviewers will include these definitions as a way to promote consistent evaluation of the applications. (See https://www.ncbi.nlm.nih.gov/books/NBK338448 for reference to the BEST Resource's glossary for the following definitions.)

Biomarker – A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers. Categories of biomarkers include: Susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, safety.

Clinical outcome assessment (COA) – An assessment of an outcome that reflects how an individual feels, functions or survives. The four types of COAs are clinician-reported, observer-reported, patient-reported, and performance outcomes.

Context of Use (COU) – A statement that fully and clearly describes the way the medical product development tool is to be used and the medical product development-related purpose of the use.

Concept – In a regulatory context, the concept is the aspect of an individual’s clinical, biological, physical, or functional state, or experience that the assessment is intended to capture (or reflect).

Validation – A process to establish that the performance of a test, tool, or instrument is acceptable for its intended purpose. For this FOA, the intended purpose should be the collection of data in a clinical trial that will be used to determine whether to move forward with the intervention being tested to a later stage trial or for regulatory approval.

  • Applications to this FOA should focus on clinical validation. Clinical validation is defined as a process to establish that the test, tool, or instrument acceptably identifies, measures, or predicts the concept of interest.
  • Biochemical and molecular biomarkers should have substantial data supporting analytical validation collected prior to submission of an application to this FOA. Analytical validation is defined as a process to establish that the performance characteristics of a test, tool, or instrument are acceptable in terms of its sensitivity, specificity, accuracy, precision, and other relevant performance characteristics using a specified technical protocol (which may include specimen collection, handling and storage procedures). This is validation of the test’s, tool’s, or instrument’s technical performance, but is not validation of the item’s usefulness.

Scope

To optimize clinical trial readiness, there needs to be sufficient understanding of the rare disease to permit design, conduct, and interpretation of rigorous clinical trials. FDA published Draft Guidance on common issues in drug development for rare diseases. This FOA is intended to support studies that address some of the issues presented in this guidance document, including the need for adequate understanding of the course of the disease and the need for sensitive and reliable biomarkers and outcome measures to be used during a clinical trial.

The R03 grant mechanism will support small research projects that can be carried out in a short period of time with limited resources. Projects must have a focus on clinical trial readiness. Projects could include:

  • Pilot or feasibility studies
  • Secondary analysis of existing data
  • Small, self-contained research projects
  • Development of research methodology
  • Development of research technology

The projects should not include clinical trials. If considering clinical trials, then please reference the NCATS website for other open opportunities.

Applicants are expected to have clinical expertise for the rare disease under study, including the capability for measuring COAs and analyzing appropriate biomarkers where applicable. Applicants should also have sufficient numbers of rare disease patients for inclusion in the study or have access to additional patients through collaboration.

Projects that are appropriate for this FOA should focus on diseases that lack critical components of trial readiness and should have candidate therapeutics that will be ready for testing in clinical trials by the time the trial readiness study is completed. For the purpose of this initiative, clinical trial readiness can include two categories of projects:

1) Those that define the presentation and course of the rare disease (e.g., secondary analysis of natural history data, retrospective projects, or cross-sectional approaches), in ways that are essential for the design of upcoming clinical trials.

2) Those that utilize sensitive, reliable, valid, and responsive tools to identify or select appropriate participants for clinical trials or to measure the effects of interventions. These tools include COA measures and biomarkers. Investigators are encouraged to use or modify existing resources, validate existing tools in specific rare disease populations, or add components to existing disease-specific tools (such as symptom scales).

This FOA will support applications for testing of biomarkers or outcome measures so that they are ready for use in multi-site studies. Biochemical or molecular biomarkers should include justification that describes accuracy, precision, analytical sensitivity, analytical specificity including interfering substances, dynamic range, and expected normal values. For imaging, radiological, or physiological biomarkers, the justification should provide preliminary data on the accuracy, reproducibility, sensitivity, and specificity as determined by study of a patient cohort (but not necessarily in the same rare disease). An appropriate study could start with a small, manageable set of well-justified candidate biomarkers, and based on data acquired during the study, be narrowed down to one or a few appropriate biomarkers to better characterize or validate for use in a clinical trial.

Examples of studies intended to be supported through this FOA include, but are not limited to, the following:

  • Studies aimed at the clinical validation of biomarkers or COAs with defined contexts of use in specific rare disease populations.
  • Proof of concept studies in an animal model of a rare disease where if successful, it would permit conduct of a clinical trial in the near term.
  • Studies to develop or incorporate patient-reported or patient-centered outcomes.
  • Studies to characterize rare disease patient cohorts regarding COA measures, biomarkers, genetic, epigenetic, or physiological factors that will be used to stratify patients or determine inclusion/exclusion criteria in upcoming clinical trials.
  • Studies to characterize rare disease patient cohorts using candidate outcome measures to establish the variability of measures as needed for accurate power calculations or to determine the appropriate duration of upcoming clinical trials.
  • Studies evaluating the responsiveness of biomarkers or COAs through the observation of patients who are receiving treatment as part of their clinical care.
  • Studies to address knowledge gaps for clinical trial planning that also pilot innovative recruitment strategies for women, minorities, and other underserved populations who would be candidates for participation in upcoming rare disease trials.
  • Studies that modify use of a tool in a specific rare disease population, such as the addition of disease-specific modules to an existing tool (e.g., disease-specific symptom scales).
  • Ancillary studies that leverage ongoing clinical studies supported through other sources of funding.

Applications investigating the following will be considered non-responsive to this FOA. Non-responsive applications will be returned without review:

  • Natural history studies aimed at broadly exploring disease pathophysiology, genetic or epigenetic mechanisms with no direct connection to an upcoming clinical trial. Studies of patient genetics or pathophysiology will be responsive only if characterization is necessary for stratifying trial participants or determining inclusion/exclusion criteria in upcoming clinical trials.
  • Studies of biomarker discovery or assay characterization.
  • Applications that propose only to maintain patient registries. NCATS and the ICs listed in Part I at NIH will not provide support to maintain or acquire additional data on study participants beyond the end of the clinical trial readiness grant.
  • Applications that request support for infrastructure to establish new clinical trial networks. Applicants should leverage existing resources such as existing rare disease-focused networks (for example, the Rare Diseases Clinical Research Network (RDCRN)).
  • Studies aimed at determining the safety, pharmacokinetics, efficacy, or effectiveness of an intervention (drug, biologic, device, etc.) in humans.

Leveraging Existing Research Resources

Applicants should leverage existing research resources for their clinical trial readiness studies. Such resources may include existing clinical research networks such as RDCRN, NeuroNEXT, or other existing networks that have successfully conducted studies of rare diseases. Also, applicants should leverage existing research resources to streamline multi-center studies, such as the SMART IRB. Leveraging the resources and support from advocacy groups, private research foundations, academic institutions, other government agencies, and the NIH Intramural program are also encouraged. Researchers interested in conducting trial readiness studies through RDCRN should contact the NCATS Scientific/Research Contact listed in the Agency Contacts section below early in the process of designing the study.

Studies that leverage the resources of ongoing clinical trials or longitudinal studies supported through other Federal or private funds are also encouraged. Researchers may consider collecting data to characterize new or improved COA measures, biomarkers, or approaches as ancillary studies to ongoing clinical trials or longitudinal studies.

Investigators are encouraged to collect the clinical data needed to apply to the FDA for qualification of biomarkers or COAs intended to be used in the regulatory review process. Researchers are encouraged to seek advice from the FDA on the development of the COA or biomarker. The FDA provides additional information about the Drug Development Tool Qualification Programs on its website.

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

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Applications can request a project period of up to 2 years and a budget for direct costs of up to $50,000 per year, but need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 2 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Government

  • 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
Foreign Institutions

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. 

Required Registrations

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.

  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
    • Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, 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.
  • eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in 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.

Letter of Intent

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
Email: lambert@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

Evidence Supporting Rare Disease Classification – The Significance section of the Research Strategy must include a paragraph with the heading, "Evidence Supporting Rare Disease Classification". If the application does not include this section, then it will be considered incomplete and will not be reviewed. This section should provide the evidence that the disease/condition being studied is classified as a rare disease; i.e., there are 200,000 or fewer patients in the U.S. This section may include one or more references confirming the prevalence of the disease/condition that is the primary focus of the research application. If the disease/condition has been granted orphan status by the FDA, provide this information in this paragraph. If it is a rare variant or subset of a more common condition, provide the rationale for focusing a trial readiness study on this variant. Describe the scientific basis for separating biomarker/clinical outcome assessment (COA) validation for this rare variant or subset from that of the common condition.

For studies involving human subjects, include a description of the sex/gender, race, and ethnicity of affected individuals and a plan to match enrollment to the demographic data. For example, data on the demographics of patients currently seen at the enrollment sites can be included, or include demographic data on patients surveyed to assess their willingness to participate in research.

Need for Clinical Trial Readiness – The Significance section of the Research Strategy must also include a subsection with the heading, "Urgent Need for Clinical Trial Readiness". If the application does not include this subsection, then it will be considered incomplete and will not be reviewed. This subsection should describe the need for conducting the trial readiness study at this time, or how the project addresses a critical barrier or bottleneck to progress toward clinical trials. Applicants should describe the clinical trial design issues (e.g., biomarker or COA validation, data for power calculations, defining inclusion/exclusion criteria, determining the duration of the trial, etc.) that will be addressed by this trial readiness study. Describe the potential impact of the proposed studies in addressing significant needs in the design and increasing the likelihood of success of upcoming clinical trials.

This section should also contain the following:

  • A brief description of the state of development of candidate therapeutics or devices for this rare disease (even if the current applicants are not involved in the development of those therapeutics/devices).
  • Timelines for the advance of therapeutics/devices to clinical trials.
  • A brief description of the clinical trial(s) that would be enabled by the results of this trial readiness study. Provide letters of support (below) from the researchers who expect to conduct upcoming trials.
  • Outline the next steps for moving into a clinical trial if the proposed study is successful—that is, provide the rationale that a clinical trial is feasible in the near future.
  • Include a brief description of the currently available COA measures and/or biomarkers. If appropriate for the proposed study, describe how the study will result in advancements over the currently available measures/biomarkers. If the current measures/biomarkers are considered inadequate or insufficiently developed for use in upcoming trials, describe their limitations and how those limitations may compromise the success of upcoming trials. If the proposed trial readiness study is ancillary to an ongoing clinical trial or longitudinal study, describe that study and provide a letter of support (below) from the study's lead PD(s)/PI(s). Explain how the trial readiness study will lead to improvements in the design of future trials above that of the ongoing study.
  • Describe any gaps in knowledge regarding the disease natural history that need to be addressed to achieve clinical trial readiness. Explain how the lack of this knowledge will compromise clinical trial design and how this study will overcome current obstacle(s).
  • Briefly describe the role of companies or voluntary health organizations that are currently engaged or potentially available for clinical trial readiness studies or clinical trials for this disease, if applicable.

Biomarkers and Their Context of Use

If biomarker validation is proposed, the Approach section of the application must contain a subsection with the heading, "Biomarkers and Their Context of Use". This section could describe each biomarker that will be tested for validation and the context of use (COU). The COU should explain how, when, and why the biomarker is to be used in a clinical trial.

Biochemical/molecular biomarkers must have analytical validation before applying for a clinical trial readiness award through this program. Applications should include a table listing each biochemical/molecular biomarker to be tested for clinical validation, the intended use (e.g., diagnostic, predictive, treatment response, pharmacodynamic), the method of the assay (e.g., mass spectrometry, ELISA, surface plasmon resonance), the sensitivity, dynamic range, and expected normal values. Other characteristics of the assay such as accuracy, precision, specifity including interfering substances, etc. should also be described in the text of this subsection. Describe what a graph of each biomarker measurement over time is expected to show (e.g., linearly decreasing measurement, sigmoidal curve, etc.) and the expected relationship of the biomarker to COA measures (e.g., inversely proportional).

For imaging, radiological, or physiological biomarkers, the rationale should provide preliminary data on the accuracy, reproducibility, sensitivity, and specificity as determined by study of a patient cohort (but not necessarily in the same disease). Describe the equipment (i.e., instrument manufacturer and model) and expertise available at each clinical site for measuring the biomarker(s). Plans for the training of personnel at each site in the use of the standardized protocols, data quality control strategies, reference standards and approaches for verifying instrument calibration at the clinical sites should also be described as appropriate.

Clinical Outcome Assessment Measures

Clinical outcome assessment (COA) measures can be clinician-, observer-, or patient-reported, or performance outcomes. If COA measure validation is proposed, applications must provide a list of each COA measure that the study aims to clinically validate. Describe the construct validity (i.e., hypothesized relationship with other disease characteristics) and content validity (i.e., extent to which the COA measures the concept of interest) for each COA measure. Describe plans for analysis of test-retest and inter-rater reliability. Describe Rasch analysis for COA measure optimization if appropriate.

Natural History Studies

Studies of the natural history of the disease may only be proposed for the purpose of developing readiness for upcoming clinical trials. If a natural history study is proposed, provide a rationale for how the natural history study will support advancement of the development of a rare disease medical product through characterization of an aspect of the disease natural history that must be addressed before a clinical trial can be planned or initiated (such as characterization of an external control group, identification of genotypic or phenotypic subpopulations necessary for defining inclusion/exclusion criteria, or other components of study design), and that the natural history study can address this characterization within the study timeframe.

Statistical Analysis Plans

A section describing the plans for statistical analysis of the data and tests for validation of biomarkers/COA or analysis of the natural history study results should be included in the application. Explain the decision for selecting the statistical analysis methods—what methods were considered; why were the proposed methods chosen. Describe sample size considerations for validating the biomarkers and COAs, or disease natural history characterization proposed. Statistical analysis of convergent validity of COA measures and biomarkers is often an important component of trial readiness studies. Describe which biomarkers and COA measures will be tested for convergent validity if appropriate for the study.

Existing Clinical Networks

Applications should briefly describe the clinical network(s) that currently exist. For example, what infrastructure is already developed to enroll and conduct clinic visits for the proposed study?

For ancillary studies, briefly describe the aims of the parent study and the timeline of the parent study relative to the proposed ancillary study. The application should discuss the additional burden to the participants of the parent study and whether consent obtained from the participants is adequate to cover the ancillary study or if additional consent must be obtained. (See also Letters of Support)

Letters of Support

Provide letters of collaboration from individuals who will contribute in a substantive, meaningful way to the scientific development or execution of the project, whether or not salaries are requested. As appropriate, letters should document access to expertise, equipment and/or patients.

For ancillary studies, provide a letter of support from the PD/PI of the parent study that includes:

  • A brief description of the aims of the parent study
  • The timeline of the parent study relative to the proposed ancillary study

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • The Resource Sharing Plan should include a timeline for publications and access to additional study data and biospecimens, where applicable. It should describe the process for evaluating requests for access to the data and/or biospecimens, and the expected time from when the request is received to when the sharing of data/biospecimens is achieved.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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

 

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:
 

The R03 small grant supports discrete, well-defined projects that realistically can be completed in two years and that require limited levels of funding. Because the research project usually is limited, an R03 grant application may not contain extensive detail or discussion. Accordingly, reviewers should evaluate the conceptual framework and general approach to the problem. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or from investigator-generated data. Preliminary data are not required, particularly in applications proposing pilot or feasibility studies.

Overall Impact

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).

Scored Review Criteria

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.

Significance

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

Specific to this FOA:

  • How strong is the rationale in the application that the disease or condition meets the criteria of being rare (fewer than 200,000 patients in the U.S. and/or documentation of FDA orphan status)?
  • If the application is for a rare variant or subset of a more common condition, how strong is the rationale that a separate clinical trial readiness activity should focus on this rare form?
  • How does the project address a significant, unmet need for clinical trial readiness, or a critical barrier or bottleneck to progress toward clinical trials? How does this application address a gap in understanding of disease natural history that would meaningfully improve knowledge needed to design and implement a clinical trial of a candidate therapeutic; or achieve outcome measure and/or biomarker clinical validation?
  • How likely are the proposed studies to establish clinically validated biomarkers and/or clinical outcome assessment (COA) measures with well-defined contexts of use, or to fill gaps in understanding the disease natural history that are currently obstacles for the design of upcoming clinical trials?
  • As appropriate, how clearly does the application describe the context of use (COU) of the biomarker or outcome measure such that it will enable the design of upcoming clinical trials?
  • How strong is the rationale that there is urgency and that there will be candidate therapeutics ready for testing in clinical trials at the time of completion of the proposed trial readiness study?
  • How strong is the feasibility that the proposed trial readiness study will permit conduct of a clinical trial in the near future?
  • How does this proposed study relate to other ongoing efforts for this rare disease? Consider whether there is overlap with ongoing efforts or missed opportunities for coordinated efforts in the same rare disease.
  • For studies that are ancillary to an ongoing clinical trial or longitudinal study, how will it advance the design of future trials beyond that of the parent study? How will the additional burden of the ancillary study affect the participants in the parent study? How does the consent obtained for participation in the parent study relate to consent for the ancillary study?

Investigator(s)

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?

Innovation

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?

Approach

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

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

Specific to this FOA:

  • How well does the application describe plans to ensure that the study is reported with transparency regarding the data collected?
  • How well characterized are the assays for biochemical or molecular biomarkers in terms of accuracy, precision, sensitivity, specificity, dynamic range, and expected normal values?
  • How well optimized and ready for implementation in a multi-site study are the methods for measuring imaging, radiological, or physiological biomarkers, and/or COAs?

Environment

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

Specific to this FOA:

  • Do the clinical sites provide access to a sufficient number of patients with the rare disease to support enrollment for the study?
  • How strong is the justification that all of the participating clinical sites have the appropriate expertise and equipment for measuring COAs and analyzing appropriate biomarkers?

Additional Review Criteria

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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.

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

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 will receive a written critique.

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

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.

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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Alice Chen Grady, M.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-2015
Email: alice.chen2@nih.gov

Tracy King, M.D., M.P.H.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-1822
Email: tracy.king@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Lauren Massey
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-496-1240
Email: lauren.massey@nih.gov

Maggie Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.

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