Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Center for the Investigation of Factor VIII (FVIII) Immune Response in Patients with Hemophilia A (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-HL-18-014

Companion Funding Opportunity

None

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

93.839  

Funding Opportunity Purpose

The goal of this Funding Opportunity Announcement (FOA) is to establish up to four Centers for the Investigation of Factor VIII immunogenicity (FVIII Centers). These Centers will utilize cross-disciplinary science and novel technologies to define the basic mechanisms involved in the development of anti-FVIII neutralizing antibodies, also known as FVIII inhibitors, in patients with congenital hemophilia A.

Applications will also include a Skills Development component to support the development of interdisciplinary research skills and expertise in the next generation of physicians/scientists in the field of hemostasis, including the entire spectrum of blood sciences. One application will be selected from the awarded FVIII Centers to provide a range of administrative support to all awardees through an Administrative Core.  

Key Dates

 

Posted Date

March 30, 2017

Open Date (Earliest Submission Date)

June 6, 2017

Letter of Intent Due Date(s)

June 6, 2017

Application Due Date(s)

July 6, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this dates.

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

November 2017

Advisory Council Review

January 2018

Earliest Start Date

March 2018

Expiration Date

July 7, 2017

Due Dates for E.O. 12372

Not Applicable

** ELECTRONIC APPLICATION SUBMISSION REQUIRED**

NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Learn more about the various submission options.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

Background and Objectives

Hemophilia A is a rare X-linked disorder affecting 1:5000 males worldwide. Hemophilia A patients with severe disease have undetectable plasma levels of clotting FVIII. As a result, they are at high risk for hemorrhaging into their muscles, joints, and organ systems and have the potential for significant morbidity and disability. Fortunately, with the widespread use of prophylactic clotting factor replacement therapies, the majority of affected children can now expect to live active lives with few bleeding episodes and a normal life expectancy. However, FVIII replacement therapy is highly immunogenic in 25-30% of the most severely affected patients. Antibodies to FVIII develop at a median age of 15 months, typically following a median of 14 exposures to FVIII. Although inherited and treatment-related risk factors have been identified, models based on these risk factors cannot accurately predict anti-FVIII antibody development in newly diagnosed patients.  

Inhibitor development diminishes or abrogates the effectiveness of therapeutically administered FVIII, and consequently represents the single-most significant obstacle to an excellent quality of life for persons with hemophilia A by substantially increasing their risk of hemorrhage-related morbidity and mortality. Furthermore, current tolerance strategies are only employed once the antibodies have developed, are difficult and costly to administer, are not based in a thorough knowledge of the immunology of FVIII antibody development, and therefore, have unpredictable outcomes. Consequently, the overall cost of care associated with this complication can exceed $700,000 yearly.

Despite significant investigator-initiated NHLBI-funded advances in FVIII biochemistry and characterization of the immune response to this immunogen, gaps in the fundamental knowledge of FVIII biology and triggers of inhibitor development remain. Novel cross-disciplinary collaborations, as well as the application of cutting edge technologies to the mechanistic study of FVIII immunogenicity are therefore critically needed. The intent of this FOA is that the establishment of FVIII Centers that facilitate interactions within and among teams of researchers from diverse scientific fields will catalyze the breakthrough research that will allow physicians to accurately predict risk for neutralizing antibody development among newly diagnosed children with severe hemophilia A; inform approaches to the design and/or delivery of less immunogenic therapeutics with the goal of inhibitor prevention in all affected individuals with hemophilia A; and guide the future safe, rapid, and targeted induction of long-term tolerance in those patients with existing inhibitors.  

The scientific goal of this funding opportunity is to generate actionable knowledge about the fundamental mechanisms of FVIII inhibitor formation that will rapidly translate into successful strategies for the prevention or elimination of FVIII neutralizing antibodies in patients with hemophilia A. Therefore, scientific programs should be bold, innovative, and multi-disciplinary, and utilize novel science and cutting edge technologies to advance our scientific knowledge of FVIII immunogenicity. The utilization of new or cutting-edge technologies such as single cell analysis, exosome analysis, genomics, transcriptomics, proteomics, metabolomics, cryo-electron microscopy, in silico modeling, and others is encouraged.

Program Structure

The program will consist of up to four FVIII Centers and one Administrative Core. Each FVIII Center will provide a Skills Development Core for new and early career researchers. It is expected that responses to the FOA will have at least three related research projects studying different aspects of an area in a coordinated manner. At least one research project must include a scientific discipline that has not traditionally been applied to FVIII immunogenicity research in the past. Traditional FVIII scientific disciplines include: immunology; biochemistry; and molecular biology. Non-traditional FVIII scientific disciplines include all other areas of scientific research, including but not limited to microbiology; glycobiology; genomics; biophysics; computational biology; and in silico chemistry.  

Examples of Research Projects

Selected research examples may include, but are not limited to:

  • Utilize genomic and trans-'omic' data to further define current models of FVIII -protein and FVIII-immune system interactions.  
  • Investigate the role of the microbiome in host predisposition to FVIII inhibitor formation.
  • Apply new knowledge about cell-specific post-translational modifications in FVIII glycan moieties to current models of FVIII immunogenicity.
  • Use FVIII structural data derived from cryo-electron microscopy for in silico modelling of FVIII immunoepitopes.

To encourage genomic analysis of FVIII inhibitor formation and identification of risk factors, investigators will have access to the NHLBI Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed) database https://www.nhlbiwgs.org/. Access to the sequencing database will depend on submission of an approved application.

Applicants are also encouraged to leverage existing resources, such as biorepositories and clinical databases within the US Hemophilia Treatment Center Network to enhance their proposed studies.

Research that would NOT be responsive to this FOA include, but are not limited to, the following:

  • Applications lacking multidisciplinary scientific teams and novel approaches/technologies.
  • Applications lacking a skills development program for new or early career investigators.
  • Applications that propose clinical trials as defined by the NIH in NOT-OD-15-015.

Investigator Meetings

Investigators from individual FVIII Centers will meet annually in Bethesda, MD to present updates on their research progress and discoveries, exchange scientific knowledge, and discuss potential collaborations. The agenda for the meetings will be determined by the Steering Committee composed of the PDs/PIs of the FVIII Centers and NHLBI Program Directors.

In addition to the annual meeting, investigators are expected to communicate with NHLBI Program staff through regularly scheduled teleconferences.

See Section VIII. Other Informationfor award authorities and regulations.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.  

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

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

NHLBI intends to commit total costs of up to $5,960,000 per year in fiscal years 2018 through 2022 to fund up to 4 awards.

Award Budget

Application budgets may not exceed direct costs of $930,000 per year in fiscal years 2018 through 2022.

Award Project Period

The maximum period of support is 5 years.   

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

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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are  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) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Page Limitations

Component Types Available in ASSIST

Research Strategy/Program Plan Page Limits

Overall

12

Admin Core (Use for Administrative Core)

6

Project (Use for Research Projects)

12

Core (Use for Skills Development Core)

6

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

  • Overall: 1 required
  • Administrative Core: required, maximum of 1
  • Research Projects: required, minimum of 3
  • Skills Development Core: required, maximum of 1
Overall Component

When preparing your application in ASSIST, use Component Type ‘Overall’.

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

SF424 (R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement  (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Facilities & Other Resources: Describe the intellectual environments (e.g., academic or other research) of the research team members and how this milieu may inspire creativity and facilitate achieving the goals of the proposed Center.

Project/Performance Site Location(s) (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research & Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application. The PD/PI must also be the Project Leader of one of the component research projects.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims:  Outline the overall goals for the proposed Factor VIII Center and its scientific focus. List the goals of the research and summarize expected outcomes.   

Research Strategy:  

Provide an overview of the proposed FVIII Center. Address all the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Significance: Describe the impact of successful completion of the proposed work, both in regards to understanding FVIII immunogenicity and in regards to the potential for translation of the work to improve therapy for hemophilia A patients.

Sub-section B. Center Framework: Describe the overarching organizational framework and vision of the proposed FVIII Centers, its scientific focus, strengths, and leadership in the research field.

Sub-section C. FVIII Center Integration: Describe how the FVIII Center and the investigational team will collectively support the overarching goal of the FVIII Center through multi-disciplinary and/or multi-institutional collaborations. In particular, if any collaboration proposed involves new interactions between research groups, discuss the means to be employed to foster collaboration and communication between the different components of the research team, and include procedures to address/resolve possible conflicts.

Sub-section D. Research Teams: Summarize the major collective strength of the research team in the proposed area of research. Without repeating information from individual biosketches, explain how the specific expertise of team members will be used to advance the proposed research program.

Applicants should provide details regarding:

  • Roles/areas of responsibility of the PDs/PIs
  • Fiscal and management coordination
  • Process for making decisions on scientific direction and allocation of resources
  • Publication and intellectual property policies (if applicable)                                    

Without repeating information from the Resource Sharing Plan, describe how data will be shared among investigators, and include a plan for communication amongst investigators. Applications should describe any prior collaborative arrangements between investigators, explain the genesis of the current application, and include the following: the anticipated unique advantages that would be gained by the research within the proposed FVIII Center; describe how the projects are interrelated, and explain how the proposed FVIII Center would enable the stated objectives of the proposed research to be addressed more efficiently and effectively than a group of individual research project grants; and indicate specific milestones that could be used to evaluate success of the project throughout the duration of funding. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

 Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application in ASSIST, use Component Type ‘Admin Core.’

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

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates
PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)
  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
  • Note: The Administrative Core director does not have to be a PD/PI.  
Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

The Administrative Core budget may not exceed $150,000 per year in direct costs. The cost of the Administrative Core should not be included in the overall budget page.

PD/PI Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 2.4 person months (20%) effort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Specific Aims: Describe the goals and planned activities of the Administrative Core.

Research Strategy:  Each application must include plans for the establishment of an Administrative Core to coordinate programmatic activities across all FVIII Centers. One Administrative Core will be selected from the funded FVIII Centers.

Applicants must address the following specific aspects:

  • Describe how the proposed Administrative Core will accomplish the objectives of the overall program.
  • Provide an operational plan and overall organizational structure for the Administrative Core
  • Describe how the Administrative Core's administrative, management, and leadership capabilities adequately provide for internal quality control of on-going research, management of day-to-day program activities, effective communication and cooperation among PD/PIs and resolution of conflicts.
  • Demonstrate that the following administrative responsibilities can be successfully performed: organizing investigator and Steering Committee meetings, arranging conference calls, coordinating cross-training of new investigators among FVIII Centers, and designing and maintaining a website for the entire program for FVIII Center investigators and Program staff to communicate and share data.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

PHS Inclusion Enrollment Report (Administrative Core)

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

Research Projects

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Research Projects)

  • Complete only the following fields:
  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project (preceded with the applicable numerical identifier (i.e., "Project 1:", or "Project 2:" or "Project 3:")
  • Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
  • Level of effort for each project leader should be at least 2.4 person months (20%).     

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

The combined budget for all Research Projects should comprise no more than $750,000 in total annual direct costs.

Each Center budget should include provisions for investigators to attend the yearly investigator's meetings. Investigators should allocate support for 1-2 representatives from each research team to travel to one grantee meeting in or near Bethesda, MD each project year.

PHS 398 Research Plan (Research Projects)

Research Strategy: Address the specific aspects indicated below using the sub-sections as defined:

Sub-section A. Individual Research Projects: Summarize the proposed research projects, their importance and interrelationship, and the rationale for their inclusions. Research projects should be proposed based on one or more of the scientific areas outlined in Section I, Scope of Scientific Research. At least one research project must include a scientific discipline that has not traditionally been applied to FVIII immunogenicity research in the past. Traditional FVIII scientific disciplines include: immunology; biochemistry; and molecular biology. Non-traditional FVIII scientific disciplines include all other areas of scientific research, including but not limited to microbiology; glycobiology; genomics; biophysics; computational biology; and in silico chemistry.

Sub-section B. Approach: Describe the bold, innovative cross-disciplinary approaches and novel technologies that will be utilized to define FVIII-specific immunologic triggers which may lead to the prevention or elimination of FVIII inhibitors in patients with congenital hemophilia A.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

PHS Inclusion Enrollment Report (Research Projects)

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

Skills Development Core

When preparing your application in ASSIST, use Component Type ‘Core.’

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

SF424 (R&R) Cover (Skills Development Core)

Complete only the following fields:

  • Applicant Information
  • Type of Applicant (optional)
  • Descriptive Title of Applicant’s Project
  • Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Skills Development Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Skills Development Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Skills Development Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Skills Development Core)

  • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
  • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
  • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
  • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   
  • Provide details regarding the research qualifications, scientific stature, previous leadership and mentoring experience, and the research track record (including NIH funding) of the proposed Skills Development Core Lead PD/PI and other participating senior scientific staff.

Budget (Skills Development Core)

Budget forms appropriate for the specific component will be included in the application package.

Applications should include up to $180,000 per year in direct costs for a skills development program. Each FVIII Center must budget for providing skills development for 5-8 early career investigators.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Skills Development Core)

Research Strategy: FVIII Centers are required to leverage their range of scientific expertise within and across Centers to create a program for skills development in interdisciplinary research and team science for the next generation of physicians/scientists in blood science. FVIII Centers are particularly encouraged to include NIH Fellowship and Career Awardees to their scientific research programs.

Skills development activities in new scientific disciplines or novel technologies could include, but are not limited to: laboratory skills training, workshops, seminar series and personnel exchanges among Centers or within Center consortia. The skills development programs will also provide early career researchers with travel support to access skills development between FVIII Centers. The Skills Development Core proposed by each FVIII Center is expected to support 5-8 early career investigators over the entire funding period. Review of the research skills development plan will be included with the scoring of the scientific application.

Applications must include a description of plans to develop and direct a basic research skills development component for early career investigators. The program should be led by a U54 PD/PI with basic research and mentoring credentials. To facilitate multidisciplinary developmental activities, active involvement by other senior PDs/PIs in the FVIII Center is encouraged.

Applicants should provide details regarding:

  • Plans to recruit and include early career investigators in their scientific research programs
  • Mentor responsibilities
  • A discussion of group activities, seminars, and forums
  • Plans to include broader trainee participation in events such as seminars, workshops, or other educational opportunities.
  • Plans to assess the success of the Skills Development Core in meeting the described goals.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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.

Section V. Application Review Information
1. Criteria

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

Overall Impact - Overall

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the FVIII Center 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 FVIII Center proposed).

Scored Review Criteria - Overall

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 FVIII Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the FVIII Center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the FVIII Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

Specific to this FOA:

Are the organizational framework, vision, and scientific focus of the proposed FVIII Center designed to enable a unique understanding of FVIII inhibitors in patients with congenital hemophilia A? Is the requirement for the FVIII Center structure to accomplish the proposed goals of the program well-articulated? Are the Center components and the investigators team well integrated to collectively support the overarching goal and the vision of the program?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the FVIII Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

Is there evidence that an appropriate level of effort of at least 2.4 person months (20%) will be devoted by the program leadership to ensure program objectives? How well do the proposed collaborations between the FVIII Center PD(s)/PI(s) and other key persons integrate to achieve the overarching research goals? 

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?

Specific for this FOA:

Are the goals of the FVIII Center original and innovative?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the FVIII Center? 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 FVIII Centerinvolves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?   

Specific to this FOA:

How well does the proposed FVIII Center take advantage of multidisciplinary approaches to promote and advance the understanding of FVIII inhibitors in patients with congenital hemophilia A? Are the overall research goals, experimental design, methods, and capabilities sound and well developed? Are effective mechanisms in place to foster strong collaborative interactions and promote “cross-fertilization” among investigators and participating institutions? Are mechanisms for facilitating sharing of samples and resources well planned or in place? 

Environment

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

Specific to this FOA:

Will the scientific environment at the participating institutions stimulate trans-disciplinary research collaborations?

Additional Review Criteria

As applicable for the FVIII Center 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Children 

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

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 Center 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 .


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.

Overall Impact Administrative Core
 

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Administrative Core 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).

 
Review Criteria - Administrative Core

Reviewers will consider each of the review criteria below in the determination of scientific merit:

  • Is the proposed Administrative Core adequate to accomplish the objectives of the overall program?
  • Are the proposed operational plan and organizational structure clearly described?
  • Do the Administrative Core's administrative, management, and leadership capabilities adequately provide for internal quality control of on-going research, management of day-to-day program activities, effective communication and cooperation among PDs/PIs, and resolution of conflicts?
  • Does the proposed Administrative Core PD/PI have experience in research administration and coordination?
  • Is there evidence of ability to provide administrative support to all the participating FVIII Centers in terms of organizing investigator and Steering Committee meetings and arranging conference calls? 
  • Is there a logical plan for designing and maintaining a website for the FVIII immunogenicity program?
Review Criteria - Cores

As applicable for the Skills Development Core, reviewers will provide an assessment of its strengths and weaknesses. In particular, the following items should be evaluated while determining scientific and technical merit; however, a separate score will not be given for these items.

For the Skills Development Core:

  • Are the research qualifications, scientific stature, previous leadership and mentoring experience, and research track record of funding (including NIH funding) appropriate for the proposed skills development program?
  • Are the content and proposed duration of the skills development plan appropriate for achieving scientific competence for early career investigators?
  • Does the program encourage the development of skills in new and cutting edge technologies, including non-traditional scientific disciplines and team science?
  • Is there a strong cross-disciplinary skills development component to learn research skills in other scientific disciplines?
  • What is the likelihood that the Skills Development Core will contribute significantly to the knowledge and scientific development of early career investigators?
Review Criteria for Research Projects

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 - Research Projects

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 there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?   

Specific to this FOA:

Does the application propose multi-disciplinary team science, including at least one scientific project that includes a scientific discipline not typically associated with FVIII immunogenicity research? In addition to the traditional scientific disciplines currently active in this field (e.g., biochemistry, immunology, molecular biology), how well does the applicant include emerging science not currently being substantially exploited in this research area (e.g., microbiology, glycobiology, genomics, biophysics, computational biology, in silico chemistry, transcriptomics, among others)?

Investigator(s)

Are the Project Leads, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

Specific to this FOA:

How well does the applicant propose to utilize novel or cutting edge technology(ies) (e.g., single cell analysis, exosome analysis, genomics, transcriptomics, proteomics, metabolomics, cryo-electron microscopy, in silico modeling)?

Approach

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

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

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 - Research Projects

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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Children 

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

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 - Research Projects

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 .

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:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

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

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 National Heart, Lung and Blood Institute Advisory Council. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information
1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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.

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

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

The PD(s)/PI(s) will have the primary responsibility for:
The Program Director(s)/Principal Investigator(s) will have the primary responsibility for: all aspects of the study, including study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NHLBI Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NHLBI Project Scientist will serve on the Steering Committee; NHLBI scientist(s) may serve on other study committees, when appropriate.  The NHLBI Project Scientist (and other cited NHLBI scientists) may work with awardees on issues before the Steering Committee, and as appropriate, other committees, for example: development and implementation of data and sample sharing plans, informed consent issues, sample collection, protocol development, quality control, data analysis and publication, and preparation and development of solutions to major problems.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:
Awardee agrees to governance, through voting and decision making, of the program through a Steering Committee.  Steering Committee voting membership shall consist of the principal investigator, site principal investigators, and the NHLBI Project Scientist.  Monthly meetings of the Steering Committee will ordinarily be held by telephone conference call.  In person meetings should be held twice yearly, once in Bethesda and once at a national conference.

Each full member will have one vote per grant and the NHLBI Program Officer assigned will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

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

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.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

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

Scientific/Research Contact(s)

Ronald Warren, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0070
Email: ronald.warren@nih.gov

Malgorzata Klauzinska, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0070
Email: malgorzata.klauzinska@nih.gov

Donna DiMichele, MD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0080
Email: dimicheledm@mail.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Gayle Jones
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-827-8040
Email: jonesgt@nhlbi.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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