National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
R21 Exploratory/Developmental Research Grant
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
This Funding Opportunity Announcement (FOA) will support meritorious exploratory research relevant to the NHLBI mission (http://www.nhlbi.nih.gov/about/org/mission) using the existing biospecimen collections that are stored in the NHLBI Biologic Specimen Repository (Biorepository), thereby maximizing the scientific value of the stored collections and providing researchers with an opportunity to generate preliminary data for subsequent research proposals.
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 |
| June 21, 2022 | June 21, 2022 | August 09, 2022 | November 2022 | January 2023 | April 2023 |
| October 19, 2022 | October 19, 2022 | December 07, 2022 | March 2023 | May 2023 | July 2023 |
| June 20, 2023 | June 20, 2023 | August 09, 2023 | November 2023 | January 2024 | April 2024 |
| October 19, 2023 | October 19, 2023 | December 07, 2023 | March 2024 | May 2024 | July 2024 |
| June 20, 2024 | June 20, 2024 | August 09, 2024 | November 2024 | January 2025 | April 2025 |
| October 21, 2024 | October 21, 2024 | December 10, 2024 | March 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.
No late applications will be accepted for this Funding Opportunity Announcement.
Not Applicable
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.
- Use the NIH ASSIST system to prepare, submit and track your application online.
- 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.
- Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
Purpose
The purpose of this Funding Opportunity Announcement (FOA) is to stimulate exploratory research relevant to heart, lung, and blood diseases and sleep disorders using the existing biospecimen collections that are stored in the NHLBI Biorepository, thereby maximizing the scientific value of the stored collections and providing researchers with an opportunity to generate preliminary data for subsequent research proposals.
Descriptions and access to the available biospecimen collections and associated datasets can be found at the NHLBI Biospecimen and Data Repository Information Coordinating Center (BioLINCC) website at www.biolincc.nhlbi.nih.gov.
Background and Objectives
The NHLBI Biorepository has served as a valuable scientific resource for nearly four decades by acquiring unique biospecimen collections from NHLBI-funded clinical studies and distributing samples to qualified investigators at no fee beyond the cost of shipping. The NHLBI Biorepository was initially established to support the need for archival collections to address emerging blood-safety concerns. The use of these collections led to several seminal contributions to public health such as establishing the viral origin of the agent responsible for non-A, non-B hepatitis (HCV) and transfusion transmissibility of HIV. Towards the end of the 1990s the scientific value, public health value and the cost-effectiveness of centrally maintaining biospecimens from unique populations and making them available to the research community were recognized as a key means to enhancing the scientific return on the Institute’s investment in the collection of these valuable resources. As a result, the NHLBI Biorepository mission was expanded to acquire quality biospecimens with potential scientific utility from NHLBI-funded clinical studies in heart, lung and blood diseases.
As of January 2022, over 4 million richly phenotyped biospecimens from 49 NHLBI-funded clinical studies are stored in the NHLBI Biorepository and are open to the scientific community through the NHLBI BioLINCC web portal at www.biolincc.nhlbi.nih.gov. The number of collections available through BioLINCC continues to grow each year. Some examples of the collections currently available are: studies in rare diseases such as A Case Control Etiologic Study of Sarcoidosis (ACCESS), the Multicenter Hemophilia Cohort Study (MHCS), Multicenter Study of Hydroxyurea (MSH) and Hemochromatosis and Iron Overload Screening Study (HEIRS); studies from unique populations such as Honolulu Heart Program (HHP), Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2), and National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC); studies from clinical trial networks such as the Acute Respiratory Distress Syndrome Network (ARDSNet) and the Blood and Marrow Transplantation Network (BMT CTN); and studies with implications for changing clinical practice such as Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Systolic Blood Pressure Intervention Trial (SPRINT). The Biorepository also includes biospecimens from several studies on people living with HIV that are suited for HIV and HIV-related research. New collections were also acquired recently including biospecimens from the Lung Tissue Research Consortium (LTRC), the NHLBI Asthma Network (AsthmaNet), the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, and Hydroxyurea to Prevent Organ Damage in Children with Sickle Cell Anemia study (BABY HUG).
Biospecimen Availability
Biospecimens available online are linked to their clinical study data in the NHLBI Data Repository and each biospecimen collection is accessed online through the parent study's BioLINCC web page. The web page provides detailed information about the parent study, research use restrictions specified by the parent study informed consent document and the number and material type of the biospecimens in the collection. Requests to search for biospecimens with specific characteristics are made using the request button at the end of the web page. The search for biospecimens fit for the proposed research question is performed by a BioLINCC and Biorepository team using the information provided by the requestor. Results are communicated back to the requestor through the BioLINCC web portal for their review and acceptance. If the search does not result in an adequate number of samples, the requestor has the opportunity to revise the criteria and continue the search. The time to complete the initial search for biospecimens varies depending on the complexity of the search parameters. Typically, responses to an initial search are provided within two weeks from submission. Additional searches will extend the search timeline. The biospecimens from successful searches are provided to qualified investigators with a funded research protocol following the procedures described on the BioLINCC website.
Biospecimen Availability Requirements
The process to determine the availability of biospecimens and obtain a Letter of Availability from BioLINCC is as follows:
Step 1. From the BioLINCC Home page at www.biolincc.nhlbi.nih.gov select the "Studies" link from the "Biospecimen and Data Resources" menu.
Step 2. Follow the search instructions on the page using specified key words and/ or material types, diseases and study type to locate potential studies with biospecimens
Step 3. Select the study(ies) of interest and review the study documents, biospecimen catalogue and the informed consent restrictions provided on the study web page to find out more about the study and resources available.
Step 4. Submit a request to BioLINCC using the "Request Specimens and/or Data" button at the foot of the selected study web page and follow the instructions on logging in to the BioLINCC web portal.
The BioLINCC and NHLBI Biorepository team will then perform a preliminary search based on the information submitted and provide the search results to the applicant. The search results will include the availability of biospecimens from the select study(ies) and may include suggestions for alternative study collections if no/or limited biospecimens are available.
If the search results do not include adequate numbers or types of biospecimens for the proposed research, then the applicant can revise the biospecimen characteristics to initiate a new search.
Applicants may request a consultation with the BioLINCC and NHLBI Biorepository team prior to or during the biospecimen search to discuss which biospecimen material types and/or study collections may be considered for their proposed research protocol. Requests for a consultation prior to submitting a search request may be made using the "Contact Us" link on the BioLINCC home page.
The request to search for biospecimens from a specific collection(s) available through BioLINCC (see Step 4 above) can be initiated at any time but must be initiated at least 21 days prior to the FOA Application Due Date that the applicant proposes to use. Given that the time to complete a search and provide a Letter of Availability varies due to the complexity of a search and/or the necessity to perform additional searches, applicants should ensure they allow adequate time for a search to be performed and confirmed.
Supplemental Biospecimens
Supplemental biospecimens from other existing collections may be used if the research question(s) cannot be fully addressed using only biospecimens available through BioLINCC. The application must justify the inclusion of other existing biospecimen collections.
Research Program Examples
The following are examples of areas of research that may be proposed under this program. These are only examples and are not meant to be inclusive. Applicants can propose other research consistent with the mission of the NHLBI.
Areas of cardiovascular research include but are not limited to:
- Identifying and validating biomarkers to help predict the risk of death or cardiovascular events (MI, stroke, heart failure, etc.) in a well-characterized population with coronary artery disease (PEACE).
- Characterizing novel serum markers of iron overload and/or its consequences (HEIRS).
- Examining the risk of major adverse events among type 2 diabetic patients during blood pressure therapy (ACCORD).
- Validation of novel biomarker-based risk prediction for thoracic aortic dissection/rupture (GenTAC).
- Determining polygenic risk for adverse outcomes in thoracic aortic disease (GenTAC).
- Explore genetic variation of syndromic thoracic aneurysmal disease (GenTAC).
- Identifying and validating biomarkers, including genetic markers, that predict the dose of anti-hypertensive drugs needed to achieve a specified BP target in a population with elevated blood pressure (SPRINT).
Areas of research in blood diseases and transfusion medicine include but are not limited to:
- Assessing immunotherapy effects on maternal-fetal HIV transmission (PACTG).
- Identifying factors contributing to the morbidity and mortality of Sickle Cell Disease (CSSCD).
- Characterizing recent or evolving distributions of viral genotypes/subtypes in the blood donor population (TTVS).
- Developing and optimizing stem cell expansion methods from cryopreserved umbilical cord blood (CBB).
- Establishing prevalence and time trends of established, emerging or newly discovered viruses, parasites or other infectious agents by application of serological and/or nucleic acid testing (NAT) (define?) analysis to one or more of the repositories established over the past 3 decades (REDS).
- Characterizing immune markers in serial pre/post transfusion recipient samples to track and study the immune consequences of transfusion (TSS/TRAP/LAPS).
Areas of research in lung diseases include but are not limited to:
- Investigating microbial translocation, peripheral inflammation and cardiopulmonary issues in HIV-infected children (P2C2)
- Identifying genetic variants that act as risk factors for susceptibility to sarcoidosis (ACCESS).
- Identifying and validating biomarkers of acute lung injury (ARDSnet).
- Determine biomarkers and genetic modifiers that predict ARDS development and clinical outcomes in critically ill patients (PETAL).
Areas of HIV-focused research within the mission of NHLBI include:
- Research on HIV-associated heart, lung, and blood comorbidities as well as HIV-associated coinfections and complications that may impact heart, lung, and blood health or conditions.
- Research toward HIV cure, including HIV persistence or potential persistence in cardiovascular, pulmonary and hematological systems and possible approaches to eliminating or eradicating such persistence.
- Research to prevent HIV transmission through blood transfusion.
- Research on cross-cutting areas in basic sciences and epidemiology that focuses on heart, lung, or blood.
Projects must propose research aims that are within the mission of NHLBI and the scientific interest areas identified in this FOA in order to be considered responsive to this FOA. Applications proposing projects with any of the following characteristics will be considered non-responsive to this FOA and will not be reviewed:
- Applications without a current Letter of Availability from BioLINCC that confirms the availability of biospecimens for the proposed research aims.
- Applications with specific aims that do not include the use of biospecimens stored in the NHLBI Biorepository from a collection(s) identified on the BioLINCC website http://www.biolincc.nhlbi.nih.gov as an "Open BioLINCC Study".
- Applications that only propose analysis of datasets. While the research proposal can include studies involving datasets, it must also use the existing biospecimen collections that are stored in the NHLBI Biologic Specimen Repository.
- Applications that propose to only use biospecimens from sources other than BioLINCC. While supplemental biospecimens from other existing collections may be used if the research question(s) cannot be fully addressed using only biospecimens available through BioLINCC, the proposal must also use biospecimens stored in the NHLBI Biorepository. The application must also justify the inclusion of other existing collections and include documentation indicating that the biospecimens are available for the proposed research aims.
- Projects that are not within the mission of NHLBI and the scientific interest areas identified in the FOA.
Non-Responsive Projects
Projects must propose research aims that are within the mission of NHLBI and the scientific interest areas identified in this FOA in order to be considered responsive to this FOA. Applications proposing projects with any of the following characteristics will be considered non-responsive to this FOA and will not be reviewed:
- Applications without a current Letter of Availability from BioLINCC that confirms the availability of biospecimens for the proposed research aims.
- Applications with specific aims that do not include the use of biospecimens stored in the NHLBI Biorepository from a collection(s) identified on the BioLINCC website http://www.biolincc.nhlbi.nih.gov as an "Open BioLINCC Study".
- Applications that only propose analysis of datasets. While the research proposal can include studies involving datasets, it must also use the existing biospecimen collections that are stored in the NHLBI Biologic Specimen Repository.
- Applications that propose to only use biospecimens from sources other than BioLINCC. While supplemental biospecimens from other existing collections may be used if the research question(s) cannot be fully addressed using only biospecimens available through BioLINCC, the proposal must also use biospecimens stored in the NHLBI Biorepository. The application must also justify the inclusion of other existing collections and include documentation indicating that the biospecimens are available for the proposed research aims.
- Projects that are not within the mission of NHLBI and the scientific interest areas identified in the FOA.
Notice of NIH's Interest in Diversity
t.
Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. See NOT-OD-20-031 and NOT-OD-22-019 for details.
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
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.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NHLBI intends to commit up to total costs of $1,155,000 per year for competitive awards in each of FY2023 through FY2025.
NHLBI intends to fund up to 10 new awards per year in FY2023 through FY2025.
Application budgets may not exceed $75,000 direct costs per year.
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.
1. Eligible Applicants
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
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- 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.
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)
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:
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
6701 Rockledge Drive, Room 7214
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Describe the specific aims of the proposed research and the relevance of the aims to NHLBI programs and priorities and one or more of the following NHLBI Strategic Goals: Understand Human Biology, Reduce Human Disease, Develop Workforce and Resources, and Advance Translational Research.
The specific aims must include the use of biospecimens stored in the NHLBI Biorepository from a collection(s) identified on the BioLINCC website www.biolincc.nhlbi.nih.gov as an "Open BioLINCC Study". Supplemental biospecimens from other existing collections may be used if the research question(s) cannot be fully addressed using only biospecimens available through BioLINCC. The application must justify the inclusion of other existing collections and include documentation indicating that the biospecimens are available for the proposed research aims.
Research Strategy:
Background/Preliminary Information
An R21 grant application need not have extensive background material or preliminary information; however, applicants must clearly describe the conceptual framework, the level of innovation, and the potential of the proposed project to significantly advance knowledge or understanding in HLB disorders. Justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
Letters of Support: The following must be submitted as Letters of Support:
A Letter of Availability from BioLINCC that confirms the availability of biospecimens for the proposed research aims must be included. Resubmitted applications must obtain a new Letter of Availability from BioLINCC. Applications without a current Letter of Availability will be considered incomplete and will not be reviewed.
If the proposed research includes the use of supplemental biospecimens (from sources other than BioLINCC), include documentation indicating that the biospecimens are available for the proposed research aims. Applications that propose to use supplemental biospecimens and are without a letter confirming the availability of the identified supplemental biospecimens will be considered non-responsive to this FOA 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, should address a Data Sharing Plan.
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.
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.
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.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit 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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or non-responsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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 R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.
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?
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?
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?
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
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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 the National Heart, Lung and Blood Institute, 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 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.
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:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
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.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten 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: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Lis Welniak, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8297
Email: welniakla@nhlbi.nih.gov
Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov
Tanya Smith
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-7072
Email: tanya.smith@nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
and Human Services (HHS)
