Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Office of The Director, National Institutes of Health (OD)

National Heart, Lung, and Blood Institute (NHLBI)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

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

National Institute on Drug Abuse (NIDA)

National Institute on Minority Health and Health Disparities (NIMHD)

Fogarty International Center (FIC)
National Center for Advancing Translational Sciences ( NCATS )

The FOA will be administered by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) on behalf of the NIH.

Funding Opportunity Title
Emergency Awards: RADx-rad Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence (PreVAIL kIds) (R61/R33 Clinical Trial Optional)
Activity Code

R61/R33 Exploratory/Developmental Phased Award

Announcement Type

New

Related Notices

August 21, 2020 - Notice of Participation in RFA-OD-20-023. See Notice NOT-TR-20-034

NOT-OD-20-144 - Notice of Intent to Publish Funding Opportunity Announcements for the RADx-rad Initiative

NOT-OD-20-121 - Notice of Special Interest (NOSI): Limited Competition for Emergency Competitive Revisions for Community-Engaged Research on COVID-19 Testing among Underserved and/or Vulnerable Populations

Funding Opportunity Announcement (FOA) Number
RFA-OD-20-023
Companion Funding Opportunity

RFA-OD-20-019 - Emergency Awards: RADx-RAD Data Coordination Center (DCC) (U24 Clinical Trial Not Allowed)

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.310, 93.865, 93.989, 93.837, 93.838, 93.839, 93.840, 93.233, 93.855, 93.846, 93.279, 93.307, 93.350

Funding Opportunity Purpose

The National Institutes of Health (NIH) is issuing this funding opportunity announcement (FOA) in response to the declared public health emergency issued by the Secretary, Department of Health and Human Services (DHHS), for the 2019 Novel Coronavirus (COVID-19). This emergency FOA provides an expedited funding mechanism as part of the Rapid Acceleration of Diagnostics-Radical (RADx-rad) initiative.

This FOA seeks to support innovative research to develop novel, new or unique and non-traditional approaches (e.g. diagnostic and prognostic biomarkers and/or biosignatures) to identify and characterize the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C) and, through a prognostic algorithm, predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2 to properly tailor his or her management and optimize health outcomes.

The funding for this initiative is provided from the Paycheck Protection Program and Health Care Enhancement Act, 2020.

Key Dates

Posted Date
August 06, 2020
Open Date (Earliest Submission Date)
August 30, 2020
Letter of Intent Due Date(s)

30 days prior to application due date

Application Due Date(s)

September 30, 2020. No late applications will be accepted for this Funding Opportunity Announcement.

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October 2020

Advisory Council Review

Not Applicable to this Emergency Initiative

Earliest Start Date

November 2020

Expiration Date
October 01, 2020
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

NIH is issuing this FOA in response to the declared public health emergency issued by the Secretary, HHS, for 2019 Novel Coronavirus (COVID-19).This emergency phased innovation funding opportunity announcement (FOA) from the National Institutes of Health (NIH) provides an expedited funding mechanism as part of the Rapid Acceleration of Diagnostics radical (RADx-rad) Initiative.This FOA willsupport innovative research to develop novel, new or unique and non-traditional approaches to 1) characterize the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C), and 2) identify and validate biomarkers and/or biosignatures for a prognostic algorithm to predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2. Such approaches will help properly tailor his or her management and optimize health outcomes.

The funding for this initiative is provided from the Paycheck Protection Program and Health Care Enhancement Act, 2020.

Background

SARS-CoV-2 is a novel coronavirus that has recently been identified as the causative agent of COVID-19, a respiratory disease that exhibits a wide range of clinical outcomes from asymptomatic and mild disease to severe viral pneumonia, Acute Respiratory Distress Syndrome (ARDS), Multisystem Inflammatory Syndrome in Children (MIS-C), acute kidney injury, thrombotic disorders, and serious cardiac, cerebrovascular and vascular complications. On March 11, the SARS-CoV-2 outbreak was classified as a pandemic by the WHO. Research is an important component of the public health emergency response before, during and after the emergency. The United States Food and Drug Administration (FDA)-authorized COVID-19 diagnostic testing is critical for slowing the spread of the virus and preventing future outbreaks. Given this, there is an urgent public health need for the National Institutes of Health (NIH) to support the development of a variety of approaches to testing.

Expanding the capacity, throughput, and regional placement of existing technologies and accelerating the development of new technologies will contribute significantly to the current national efforts to curb the COVID-19 pandemic. To help meet this need, NIH launched the Rapid Acceleration of Diagnostics (RADx) program to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 testing. The RADx program is a national call for scientists and organizations to bring their innovative ideas for new COVID-19 testing approaches and strategies.

As a part of this program, the NIH developed the RADx Radical (RADx-rad) initiative. RADx-rad will support new, or non-traditional applications of existing approaches, to enhance their usability, accessibility, and/or accuracy. RADx-rad will be centrally aligned and coordinated to harmonize the data collection, storage, and management, providing an opportunity to further explore and identify additional approaches to understand this novel virus. Beyond the current crisis, it is anticipated that the technologies advanced through RADx-rad may also be applicable to other, yet unknown, infectious agents.

To centrally align and coordinate RADx-rad projects to harmonize the data collection, storage, and management, the Data Coordination Center (DCC) will be established to serve as the “hub” in a hub-and spoke organizational framework within the funded RADx-rad research and development projects serving as spokes. In turn, the DCC will serve as a spoke in the larger NIH RADx initiative by providing de-identified data to an NIH-based data hub. NIH expects that all projects funded under this FOA will actively coordinate, collaborate, and share data with the RADx-rad Data Coordinating Center, as allowed, and with considerations under tribal IRB processes, as appropriate. The RADx-rad DCC will provide support and guidance to RADx-rad awardees in the following three areas: (1) Administrative Operations and Logistics, (2) Data Collection, Integration and Sharing, and (3) Data Management and Use. The DCC will develop (and revise as necessary) a framework for standards, metadata and common data elements that apply to all types of data gathered by RADx-rad awardees in order to maximize potential for longitudinal research, integration with other RADx data, and for evaluation of RADx-rad program impact. The DCC will assist awardees in identifying and obtaining data from public sources (e.g., Census data, Area Deprivation Index, etc.), electronic health records (EHR), administrative data, and others as needed. The DCC will coordinate quality control, data curation, and analyses, and provide tools to monitor progress, performance, and use of the curated data. The DCC will create a mechanism to support harmonizing with other large-scale COVID-19 research efforts and will participate in trans-NIH efforts to support scientific collaboration and data-sharing, evaluation of progress towards sustainable infrastructure, partnership and rapid dissemination of RADx findings.

NIH requires that all projects funded under this RFA will actively coordinate, collaborate, and share data with the RADx-rad Data Coordinating Center, as allowed, and with considerations under tribal IRB processes, as appropriate. Researchers applying to this funding opportunity are strongly encouraged to review the Data Coordinating Center (DCC) funding opportunity (RFA-OD-20-019).

  • To the extent possible, data acquisition, collection, and curation strategies should be coordinated with the DCC guidance for annotation and benchmarking of data, including obtaining appropriate consent for data sharing and implementation of the schemas proposed under the ABOUT ML effort (“Annotation and benchmarking on understanding and transparency for machine learning lifecycles”; available at https://www.partnershiponai.org/about-ml/).
  • In order to maximize progress and successful outcomes, recipients are expected to participate in DCC-organized activities, including regular (e.g., monthly) progress meetings with individual or subsets of awardees, and twice annual meetings with all RADx-rad awardees

To maximize research and rapidly implement approaches to address the COVID-19 pandemic, comparisons across datasets or studies and data integration are essential to collaboration. Projects funded through this RFA are strongly encouraged to use the following resources as applicable:

  • Data Harmonization for Social Determinants of Health via the PhenX Toolkit: Investigators involved in human-subject studies are strongly encouraged to employ a common set of tools and resources that will promote the collection of comparable data on social determinants of health (SDOH) across studies. In particular, studies with human participants should incorporate SDOH measures from the Core and Specialty collections that are available in the Social Determinants of Health Collection of the PhenX Toolkit (www.phenxtoolkit.org).
  • A trans-NIH working group is making existing COVID-19 survey items and investigator contact information publicly available through two NIH-supported platforms: the NIH Public Health Emergency and Disaster Research Response (DR2) [https://dr2.nlm.nih.gov/] and the PhenX Toolkit [https://www.phenxtoolkit.org/index.php]. Researchers addressing COVID-19 questions, whether population-based or for clinical research, are strongly encouraged to consider these COVID-19 specific survey item repositories and select existing survey items or protocol modules currently being fielded.

Project Details

Despite substantial numbers of children becoming infected with SARS-CoV-2 globally, most have had mild COVID-19 clinical illness unless co-morbidities were present. Initially, the risk of severe disease or mortality was thought to be a concern exclusively for adults and the elderly. However, within the past 3 months, reports from Europe and the US of a multisystem inflammatory syndrome in children (MIS-C) associated with prior SARS-CoV-2 exposure and/or infection of varying severity, including shock and death, have increased attention to the varied pediatric manifestations of the infection and its post-infectious complications. Significantly, MIS-C occurs in previously healthy children who may have initially had only mild manifestations or no symptoms at all. In addition, an increase in the number of cases of Kawasaki Disease (KD) has occurred and is thought to also be associated with SARS-CoV-2 infection. Typical KD, which occurs many-fold more often in Japan than in the US, has been known for decades. Its underlying mechanism is unknown, but it has been suspected that an as of yet unidentified ‘immune trigger’ leads to the phenotype. Variability in clinical presentation and overlap with a continuum of other disease manifestations have hindered robust investigations into its immunopathogenesis, preventing identification of reliable and accurate diagnostic and other markers of disease severity and progression. The milder presentation of SARS-CoV-2 in children characterized by minimally symptomatic or asymptomatic disease is particularly challenging and further complicates prompt identification of children who may progress to the more severe cascade of post-infectious inflammation-mediated organ damage and dysfunction representative of MIS-C.

The new working case definition of MIS-C from the CDC is 1) An individual aged < 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (=2) organ involvement (cardiac, renal, respiratory, hematologic, GI, dermatologic, or neurological; 2) No alternative plausible diagnoses; 3) Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or exposure to a suspected or confirmed COVID-19 case within 4 weeks prior to the onset of symptoms. Thus, to answer whether there is a spectrum of disease that may be potentiated or separately provoked by SARS-CoV-2 – that is, SARS-CoV-2 immune-mediated fever with cytokine release versus SARS-CoV-2 triggered KD or, SARS-CoV-2 triggered shock - it is imperative to swiftly characterize that spectrum and robustly inform the clinical and research community whether and how to diagnose and to predict the risk of MIS-C.

While research findings on COVID-19 have yielded important new scientific information with unprecedented reach and expedience, fundamental questions remain unanswered about the natural history and pathobiology of SARS-CoV-2 infection in children that may help provide important clues on host-pathogen interactions with potential prognostic power to predict optimal outcomes:

  • Why do children have milder illness?
  • Are there differences in childhood biology (e.g. gender, puberty, etc.) that contribute to illness severity?
  • Are there genetic host differences associated with different disease severity phenotypes, including MIS-C?
  • Are there innate mucosal, humoral, cellular and other adaptive immune profiles that are associated with reduced or increased risk of progressive disease, including previous coronavirus infections?
  • Will SARS-CoV-2 reinfection cause worse disease as seen with antibody dependent enhancement (ADE) in other viral infections (e.g. Dengue)? Will future vaccines carry a risk of the ADE phenomenon?
  • Does substance use (e.g. nicotine, marijuana) exacerbate or trigger MIS-C through immune activation?

To address these and other vital questions in this emerging and potentially devastating health threat among children, there is a critical and urgent need to develop novel, new or unique and non-traditional approaches to 1) characterize the spectrum of SARS CoV-2 associated illness in children, including MIS-C, and 2) identify and validate biomarkers and/or biosignatures for a prognostic algorithm to predict the longitudinal risk of disease severity after a child is exposed to and may be infected with SARS-CoV-2 to properly tailor his or her management and optimize health outcomes. Such prognostic approaches would bring an evidence base to inform decisions about safely operating schools.

Research Objectives and Scope

This initiative intends to focus on novel, nontraditional approaches to find cases of SARS-CoV-2 associated illness in children to promptly address the emerging health threat posed by MIS-C and will require access to well-characterized cohorts of children along the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C), and to their biospecimens and data. To be successful, the development of such approaches must be multifaceted and include novel testing strategies and technologies (e.g. diagnostic and prognostic biomarkers and/or biosignatures), used alone or in combination (e.g. artificial intelligence [AI]-based algorithms) to rapidly diagnose and characterize MIS-C associated with SARS-CoV-2 and to accurately risk-stratify and predict disease severity throughout exposure and/or infection and throughout the course of illness. Ideal approaches will also include a longer-term vision of advancing the development of assays, technologies and strategies that are Real-time connected, Easy to collect specimens, Affordable, Sensitive, Specific, User-friendly, Rapid, Equipment-free and Delivered to children who need them (REASSURED). Collectively, these will accomplish the following overarching research objectives:

  1. Rapid diagnosis and characterization of the spectrum of MIS-C associated with SARS-CoV-2; and,
  1. Accurate risk-stratification and prediction of severe disease (MIS-C) outcomes along the spectrum of SARS-CoV-2 exposure and/or infection and throughout the course of illness.

These approaches, strategies and technologies that may lead to an accurate, reliable and validated MIS-C prognostic algorithm to enhance the treatment of children must ideally include all or as many of the following areas, as possible:

1. Genetics, Omics and Other Biomarkers

A variety of host and pathogen-specific characteristics have been associated with COVID-19 related health outcomes, including HLA, ABO blood groups, H antigen secretor status, serum proteins, lipids and metabolites, and virus clades and subtypes. Additionally, immunologic characteristics recently identified among COVID-19 patients suggest biophysiological perturbations not only from associated immune activation and dysregulation, but also from potential viral-mediated immunosuppression. Effects from perturbations can manifest not only systemically, but also locally at mucosal tissues necessitating a strategic approach to sample collection and analysis including saliva, nasopharyngeal or oropharyngeal secretions, sputum, bronchoalveolar fluid, stool, blood, plasma, serum, urine, and/or sweat. Strategies for identifying a prognostic biomarker signature could include various ‘omics’ platforms including but not limited to genetic, genomic, transcriptomic, proteomic and metabolomic. Artificial intelligence and machine learning algorithms can be employed to screen and identify candidate biosignatures diagnostic of MIS-C and with prognostic potential that will then need to be validated.

2. Viral Dynamics and Immune Profiling Studies

Advances in rapid point-of-care testing have demonstrated the capacity for portable and inexpensive diagnostics for viral infections. The rapidly evolving fields of molecular diagnostics, biotechnology, synthetic biology and other related research areas will be useful in developing innovative approaches that allow direct detection of SARS-CoV-2 in a self-testing platform. Similarly, innovative self-testing approaches may facilitate the identification of an early and evolving immune response to the virus and determine potential immune correlates of protection, especially among minimally symptomatic children with COVID-19 or among asymptomatic carriers. Finally, a combination of novel direct antigen and antibody detection strategies will be needed to comprehensively characterize the trajectory of viral shedding and inform risk of onward transmission events and characterize the immunopathogenesis throughout the spectrum of exposure to SARS-CoV-2 to acute and convalescent infection in infants, children and adolescents. Sample collection and analysis here may similarly require saliva, nasopharyngeal or oropharyngeal secretions, sputum, bronchoalveolar fluid, stool, blood, plasma, serum, urine, and/or sweat.

3. Digital Health Platforms Leveraged for Children

The rapid proliferation of data science technologies and platforms in helping focus and implement successful COVID-19 containment and mitigation strategies can be leveraged to inform risk profiles that may have diagnostic and prognostic potential for children with MIS-C. Biosensors incorporated with mobile technology and access to pediatric EHRs could help correlate data and assess temporal relationships. Cloud computing can be implemented for storage and analysis, sharing with local health agencies to track cases of MIS-C.

4. Artificial Intelligence Platforms

Artificial intelligence (AI) and machine learning can be leveraged to integrate and analyze data in real-time and facilitate the identification of a biosignature with prognostic potential to establish reliable algorithms for characterization of MIS-C and predicting severe disease outcomes. To accomplish this, strategies will be needed that employ deep learning to expeditiously interrogate a variety of data sets (e.g. signs and symptoms, physical findings, diagnoses, laboratory, radiology and other images, and mobile health data, etc.) to recognize, identify and iteratively analyze specific patterns of disease presentations or manifestations of MIS-C. AI algorithms can diagnose and help tailor medical care and treatment plans to optimize pediatric health outcomes in MIS-C and can be validated in clinical trials or through other methods.

Development of such technologies is expected to require collaboration among experts in the fields of virology, biotechnology (e.g., microfluidics, bioengineering, synthetic biology, nanotechnology, and/or manufacturing) and bioinformatics, as well social and behavioral science. While a main focus of the studies should be on biomarkers and signatures of MIS-C, ancillary studies related to development and integration of technologies for sample preparation and/or sample readout are also expected. Applicants who include a consultation milestone with FDA to pursue Pre-EUA and EUA request mechanisms for novel coronavirus test development at an appropriate time during either the R61 or R33 phase, depending on the stage of project will receive high program priority. Applicants are not required to consult with the FDA during the R61 phase but are encouraged to include a consultation as one of their R61 milestones if the project is sufficiently advanced that an EUA request is expected during the R33 phase.

Research activities from this initiative will complement other NIH-wide initiatives to address a critical knowledge gap about the contributing factors associated with increased susceptibility to MIS-C and how these data can be used in real-time to implement risk-stratified management strategies. This initiative also intends to leverage relevant innovations from other NIH Institutes (e.g. NIBIB’s POCTRN), and research platforms supporting well-characterized cohorts of children along the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C), and their biospecimens and data, as appropriate. Such cohorts may be available through the NIH RADx-UP-funded [NOT-OD-20-121] large-scale networks, consortia and centers focused on COVID-19 testing in underserved and vulnerable children and adolescents and/or other NIH-funded networks and studies focused on MIS-C and/or SARS-CoV-2 infection and complications in children.

International research partners may be eligible for inclusion, if appropriate, to increase the sample size and participant diversity, which affects the host genome, genetic factors that involve the immune system, environmental and sociocultural factors, and other co-factors. In addition, NIH intramural investigators would be eligible and encouraged to contribute relevant expertise and resources to synergize with this program.

Applications nonresponsive to terms of this RFA will be withdrawn without review. The following types of projects would generally not be appropriate and may be deemed non-responsive:

  • Applications that propose the use of a data management and analysis platform other than the RADx-rad DCC U24.
  • Applications focused exclusively on the early development of diagnostic testing methodologies.
  • Applications that are focused exclusively on sample preparation, target enrichment, and/or readout without substantial emphasis on virus or biomarker detection.
  • Applications lacking clearly described Go/No-Go Transition Milestones.
  • Applications on the multisystem inflammatory syndrome associated SARS-CoV-2, but without an exclusive focus on infants, children and adolescents (<21 years).
  • Projects that do not have an infrastructure to rapidly report study findings and impact to the DCC.

Phased Innovation Awards

This funding opportunity will use the R61/R33 phased award mechanism. Support will be provided for up to two years for the R61 phase, and up to two additional years of support may follow for the R33 phase.

The R61 phase is for high-risk, high-impact, milestone-driven exploratory/feasibility studies. Preliminary data are not required for the R61 phase. However, appropriate theoretical justification and hypotheses should be provided as evidence that the proposed project is feasible and well-designed for the intended purpose. The use of milestones for the R61 phase will guide the potential transition to the R33 phase.

The R33 phase is for expanded discovery and development of biomarkers and/or biosignatures, such as optimization of performance specifications and validation testing of prognostic algorithms against appropriate comparison conditions.

Applications should include research plans and budgets for both the R61 and R33 phases. The clarity and completeness of the R61/R33 application, including specific goals and Transition Milestones, are critical. The Transition Milestones are essential components of the application and must be specific, quantifiable, scientifically rigorous, and meaningful, if achieved. They will serve as objective metrics of success in the R61 phase and will guide the potential transition to the R33 phase.

Before the end of the R61 phase, awardees will submit the R33 transition package, which includes the R61 progress report describing in detail the progress towards the initial R61 milestones, and an updated description of the research proposed for the R33 phase based on completion of the R61 milestones. These materials will be evaluated by NIH Program staff. Programs that consult with the FDA prior to the transition review will receive high program priority at the transition. Transition to the R33 phase is neither automatic nor guaranteed; funding decisions will be based on the successful completion of pre-defined milestones, program priorities, and availability of funds. Grants selected for continued funding will be transitioned to an R33 award without the need to submit a new application

Leveraging Existing Research Resources: Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. NIH has developed innovative solutions that will improve the efficiency, quality, and impact of the process for turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public through programs such as: NCATS Clinical and Translational Science Awards (CTSA) Program, Research Evaluation and Commercialization Hubs (REACH), Small Business Education and Entrepreneurial Development (SEED) for assistance in proof of concept and commercialization of a marketable product. Applicants are encouraged to leverage all available internal (e.g., home institutional) and external (e.g., external institutional, NIH, and/or NIDCR and NCATS) resources to identify clinically relevant COVID-19 patient populations

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

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?
Optional: Accepting applications that either propose or do not propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NIH OD intends to commit an estimated total of $5,000,000 in fiscal year 2021 to fund approximately 5-6 awards.

Award Budget

Application budgets are limited to $500,000 in direct costs per year in the R61 phase and $1,000,000 in direct costs per year in the R33 phase. All F&A costs are excluded from this limit. Requested budgets should 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 for an application submitted in response to this FOA cannot exceed 4 years. Applicants may request up to two years of support for the R61 phase, and up to two years of support for the R33 phase.

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 Governments

  • 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)

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. In the case of Emergency awards, if the applicant is unable to comply with the requirement to complete and maintain SAM registration at the time of application submission, contact the agency immediately.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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.

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. 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)

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 Guideexcept 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:

Bill G. Kapogiannis, MD
Telephone: 301-402-0698
Fax: 301-496-8678
Email: kapogiannisb@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 Budget

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

  • Budgets for both the R61 and R33 phases must be included in the application.
  • Within the budget justification section, for each budget year provide a justification indicating whether costs are for the R61 or R33 phase.
  • Awardees must budget to attend twice annual meetings with other RADx-rad awardees focused on study initiation, progress and study results approximately at the start and middle of each funding year, respectively.
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:

Specific Aims: The specific aims for both the R61 phase and the R33 phase should be included on the single Specific Aims attachment. Include headers indicating the R61 specific aims and the R33 specific aims.

Research Strategy: In preparing the R61/R33 application, investigators should consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application with regards to specific goals and the feasibility of each phase and the Transition Milestones are critical. Within the Research Strategy section, applicants should include:

  • A detailed description of access to well-characterized cohorts of children along the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C), and to their biospecimens and data. Such cohorts may be available through the NIH RADx-UP-funded [NOT-OD-20-121] large-scale networks, consortia and centers focused on COVID-19 testing in underserved and vulnerable children and adolescents and/or other NIH-funded networks and studies focused on MIS-C and/or SARS-CoV-2 infection and complications in children. While access to these cohorts is relevant to the entire project, it is critical to have demonstrated successful and productive collaborations with investigators who are leading such cohorts to justify transition in to the R33 phase.
  • A clear description of how the proposed research addresses the research objectives of this FOA, including how the (up to) 4 research areas will be integrated and interact to achieve a cohesive and innovative research program that will accomplish the objectives.
  • A description of how the proposed, multifaceted and non-traditional approach(es) address(es) the desirable general characteristics and appropriate performance parameters for ideal diagnostic and prognostic biomarkers and/or biosignatures of MIS-C, as described in the research objectives of this FOA.
  • Clearly labeled sections (separated by phase) to describe each R61 and R33 phase along with timelines, as appropriate. Do not repeat information or details that are described in the R61 section in the R33 section unless they differ substantially.
  • A description of how the additional requirements, including the leveraging of and collaboration with the RADx-rad DCC U24 infrastructure, will be incorporated across the project and in both phases
  • Recipients are expected to work with the RADx-rad Data Coordinating Center (DCC) to submit common evaluation metrics on COVID-19 testing-related outcomes and implementation to the DCC. Recipients should identify a dedicated unit responsible for these data reporting activities
  • Applications must include milestones towards progress and a timeline for completion. The timeline must include plans for regular reports of progress to be submitted to the DCC. These reports will include a description of how these progress milestones for each of the R61 and R33 phases relate to the Transition Milestones described in detail below under “Phased Innovation Awards”.
  • Projects must include an evaluation plan demonstrating how the proposed COVID-19 diagnostic strategies/activities will be assessed for effectiveness and impact.
  • Recipients are expected to obtain and retain personal identifiers on all research participants where it is not prohibited (i.e., Tribal data sovereignty) for future longitudinal follow-up and to be leveraged for intervention research. Data collected from this program will be protected by a Certificate of Confidentiality.
  • Recipients must include measures and reporting of relevant testing implementation outcomes, to inform future community, local, state, and federal policies
  • As with all NIH supported research, details regarding human subjects research are expected, including data safety and monitoring plans and, if needed, plans for a Data Safety and Monitoring Board (DSMB). Studies that have a DSMB are expected to coordinate with DCC for DSMB activities
  • Recipients are expected to disaggregate study results by sex/gender; race and ethnicity; age and other relevant demographic factors, and to consider intersectionality as appropriate.
  • Include a clearly labeled section for the Go/No-Go transition milestones for the R61 phase. In this section, provide milestones for completion of the R61 phase of the project, the suitability of these specific milestones for assessing success of the R61 phase, and the implications of the successful completion of these milestones for the proposed R33 phase. These milestones should be specific, quantifiable, scientifically rigorous, meaningful if achieved, and not a simple restatement of the R61 specific aims. Applicants are required to use Gantt charts or other similar graphics to support the timelines and the Go/No-Go Transition Milestones.
  • Include progress milestones and a timeline for completion for each year of the entire R61/R33 project. The timeline must include plans for regular reports of progress to be submitted to the DCC. The progress milestones which apply to each phase (R61 and R33) of the project should be clearly labeled within the Research Strategy section and distinguished from the Go/No-Go transition milestones. These progress milestones should also use Gantt charts or other similar graphics.Additionally, feasible and appropriate plans to submit data, data collection instruments, and outcomes/products to the DCC should be included in the milestones. The applicant must acknowledge that they will include testing implementation outcomes in their reporting to the DCC, to inform future community, local, state, and federal policies.
  • Evaluation Plan: Projects must include an evaluation plan demonstrating how the proposed COVID-19 diagnostic strategies/activities will be assessed for effectiveness and impact.
  • The applicant must acknowledge that they will coordinate with the DCC for DSMB activities, if their study has a DSMB.
  • The applicant must acknowledge that they will obtain and retain personal identifiers on all research participants where it is not prohibited (i.e., Tribal data sovereignty) for future longitudinal follow-up and to be leveraged for intervention research.

Note: Applications lacking clearly described timelines for both phases, as well as the Go/No-Go Transition Milestone will be considered incomplete and will not be reviewed.

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, must address a Data Sharing Plan
  • It is required that awardees will rapidly disseminate data, results, and analyses to the broader scientific community, using existing public repositories whenever possible when not limited by Tribal data sharing policy, as a foundation for further study.
Appendix:

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-definedclinical 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.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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.

Pre-award costs may be incurred from January 20, 2020 through the public health emergency period and prior to the date of the federal award.

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 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

In addition, for applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

For this particular announcement, note the following:

The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical research. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate theoretical justification and hypotheses for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data, as evidence that the proposed project is feasible and well-designed for the intended purpose. The use of specific, quantifiable, scientifically rigorous milestones for the R61 phase will guide the potential transition to the R33 phase. The R33 phase is for expanded discovery and development, such as optimization of performance specifications and validation testing, with appropriate comparison condition. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases.

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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Does the plan provided by the investigators give a clear description of how the (up to) 4 research areas will be integrated and interact in a cohesive and innovative research program to accomplish the objectives?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

Does the approach have the desirable general characteristics for the proposed diagnostic and prognostic biomarkers and/or biosignatures of MIS-C, as stated in the FOA? Is sufficient information provided on the performance parameters of the proposed technologies and/or strategies?

Is there sufficient quality and detail in the description of how the investigators will access and leverage well-characterized cohorts of children along the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome in children (MIS-C), and their biospecimens and data?

Is there an adequate description of how the investigators will collaborate with the required centralized data management and coordinating infrastructure of the RADx-rad DCC? How feasible and appropriate are the plans to submit data, data collection instruments, and outcomes/products to the DCC?

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?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Transition Milestones

Are the proposed Timelines for both the R61 and R33 phases of the project and the Transition Milestones specific, quantifiable, scientifically rigorous, feasible, and meaningful, such that if achieved, they would demonstrate the project will have high likelihood of achieving the R33 research goals with the study developed in the R61 phase?

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of thecategories 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

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 for sharing with the community, 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 the Center for Scientific Review (CSR), using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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. 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.
  • Applications that include plans to rapidly make data available to the research community, when not limited by Tribal data sharing policy.

3. Anticipated Announcement and Award Dates

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm.

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

NIH is requiring data sharing for all COVID-19 projects, where it is not prohibited (i.e., Tribal data sovereignty). The NIH expects and supports the timely release and sharing of final research data from NIH-supported studies for use by other researchers to expedite the translation of research results into knowledge, products, and procedures to improve human health. Grantees are expected to work with the RADx-rad DCC to submit common evaluation metrics on COVID-19 testing-related outcomes and implementation to the DCC. Grantees should identify a dedicated unit responsible for these data reporting activities. NIH expects that all projects funded under this FOA will actively coordinate, collaborate, and share data with the RADx-rad DCC, as allowed, and with considerations under tribal IRB processes, as appropriate. Researchers applying to this funding opportunity are strongly encouraged to review the DCC funding opportunity. To the extent possible, data acquisition, collection, and curation strategies should be coordinated with the DCC guidance for annotation and benchmarking of data, including obtaining appropriate consent for data sharing and implementation of the schemas proposed under the ABOUT ML effort (“Annotation and benchmarking on understanding and transparency for machine learning lifecycles”; available at https://www.partnershiponai.org/about-ml/). Grantees are expected to participate in DCC-organized activities, including regular (e.g., monthly) progress meetings with individual or subsets of awardees, and twice annual meetings with all RADx-rad awardees.

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, 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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 “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, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Funds awarded using appropriations provided by the “Paycheck Protection Program and Health Care Enhancement Act, Public Law 116-139” will be issued in unique subaccounts in the HHS Payment Management System and will require separate financial reporting from any other funds awarded.

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 agreementsare 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 threatensubmission 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)

Bill G. Kapogiannis, MD
Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0698
Email: kapogiannisb@mail.nih.gov

Peer Review Contact(s)

Alexander Politis, PhD
Center for Scientific Review
Telephone: 301-435-1150
Email: politisa@csr.nih.gov

Financial/Grants Management Contact(s)

Bryan S. Clark, MBA
Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@mail.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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