Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Resources to Assist Investigations in Primary Immunodeficiency Diseases (U24)
Activity Code	U24 Resource-Related Research Projects Cooperative Agreements
Announcement Type	Reissue of RFA-AI-08-066
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-AI-13-054
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856
Funding Opportunity Purpose	The purpose of this funding opportunity announcement (FOA) is to provide resources in support of advancing research on primary immunodeficiency diseases. These resources are currently (1) a registry of individuals with primary immunodeficiency disease; (2) a repository of cells and other materials to aid primary immunodeficiency disease research; and (3) educational opportunities to provide training, disseminate information, and encourage collaborative research on primary immunodeficiency disease. Applicants must propose plans to maintain and improve these resources.

Posted Date	December 11, 2013
Open Date (Earliest Submission Date)	March 17, 2014
Letter of Intent Due Date(s)	March 17, 2014
Application Due Date(s)	April 17, 2014, 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.
AIDS Application Due Date(s)	April 17, 2014, 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.
Scientific Merit Review	July 2014
Advisory Council Review	October 2014
Earliest Start Date	February 2015
Expiration Date	April 18, 2014
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this funding opportunity announcement (FOA) is to maintain, improve, and develop the Primary Immunodeficiency Diseases Research Resources (PIDDRR), which are currently provided by the United States Immunodeficiency Network (USIDNET). The resources and activities fall into three broad categories:

• Registry: Maintain the current registry of individuals with primary immunodeficiency diseases and enroll newly affected individuals. The types of data collected may be expanded and refined. Collaborations with other registries involved in primary immunodeficiency diseases are encouraged.
• Repository: Maintain the current repository of cell lines and add additional cell lines, reagents, and other materials of value to the research community.
• Education and Training: Provide training and educational opportunities, disseminate information, and encourage collaborative research on primary immunodeficiency diseases.

These resources and activities may be expanded and additional reagents and other materials may be developed under an award made in response to this FOA to support research on primary immunodeficiency diseases.

Primary immunodeficiency diseases (PIDD) result from inherited defects in the immune system. More than 150 PIDD and 120 different genes underlying these diseases have been identified (Al-Herz et al. 2011).  Some primary immunodeficiencies are profound, reducing resistance to many infectious pathogens, and are often detected early in life. Other primary immunodeficiencies are incomplete, leaky , reducing resistance to only a few pathogens, and may be detected only in adulthood or remain undetected. Although individual PIDD are rare, collectively they have been estimated to affect 0.1% of the population in the United States (Boyle & Buckley 2007). Another study measured an incidence of approximately 10 per 100,000 person-years in a Minnesota population (Joshi et al. 2009). In addition to the potential therapeutic benefits to affected individuals, identifying and understanding the molecular causes of PIDD provide unique insights into the functioning of the human immune system.

A registry of individuals with chronic granulomatous disease (CGD) was established in 1992 with support from the National Institute of Allergy and Infectious Diseases (NIAID). The registry was expanded to include information on individuals with other PIDD, including X-linked agammaglobulinemia (XLA), hyper-IgM syndrome (HIGM), severe combined immunodeficiency disease (SCID), common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome (WAS), DiGeorge syndrome (DGS), and leukocyte adhesion deficiency (LAD). The registry had enrolled 3,025 patients as of the end of 2012.

In 2003, the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD) awarded a contract to the Primary Immunodeficiency Diseases Research Consortium to maintain and develop resources for primary immunodeficiency disease research. These resources included the PIDD registry described above, a repository of cell lines, educational and training opportunities, and funds for pilot research projects. In 2007, the pilot research projects were removed from this contract and competed through separate funding opportunities that were renewed in 2010. In 2008, support for the registry, repository, and education roles were competed as a cooperative agreement (RFA-AI-08-066) and awarded to the Immune Deficiency Foundation to support USIDNET. This FOA is for the continued support of the registry, repository, and education activities of the PIDD Research Resource (PIDDRR).

PIDDRR Registry Activities

The current registry securely collects, maintains, and provides to qualified researchers information on individuals with primary immunodeficiencies, including:

• Common variable immunodeficiency (CVID)
• Hyper Immunoglobulin-M syndrome (HIGM)
• DiGeorge Syndrome (DGS)
• X-linked agammaglobulinemia (XLA)
• Leukocyte adhesion deficiency (LAD)
• Chronic granulomatous disease (CGD)
• NF-kB essential modifier deficiency (NEMO)
• Wiskott-Aldrich syndrome (WAS)
• Severe combined immunodeficiency disease (SCID)
• SCID adenosine deaminase deficiency (SCID/ADA)
• Complement deficiencies
• Others (see Al-Herz et al. 2011)

The registry had 3,025 patients enrolled as of the end of 2012.

The registry data must be collected and entered only in accordance with a protocol approved by a registered institutional review board (IRB). The registry must protect the privacy of those enrolled in compliance with HIPAA rules and guidance. Physicians, their assistants, and registry staff may submit information for the registry on paper forms or through a secure web-based system. A core form should be used to capture a common dataset for all patients. Disease specific forms should be used to capture additional information specific to those conditions. The current core and disease-specific registration forms are available on the USIDNET website.

Database queries are currently submitted through a web form linked on the USIDNET home page. Investigators from academic, hospital, industry, and patient advocacy organizations have used the USIDNET registry information to answer specific questions. Registry information has also helped identify physicians who are caring for individuals with specific characteristics. The results have been used for papers published in peer-reviewed journals, manuscripts, abstracts, and grant applications.

PIDDRR Repository Activities

The repository currently has 86 cell lines representing 18 different primary immunodeficiencies. Of these, 46 de-identified cell lines representing 15 different PIDD are available from the USIDNET collection maintained by the Coriell Institute. Additional cell lines from individuals with PIDD are available in other collections housed at Coriell Institute, for example, the NIGMS Human Genetic Cell Repository. A curated listing of antibodies for diagnosis or investigation is being developed by the current grantee. Additional biological specimens of value for the research community may be developed with support of this award.

PIDDRR Educational and Training Activities

With NIAID funds, USIDNET has provided partial support for:

• An annual scientific conference typically held in conjunction with the Clinical Immunology Societies (CIS meeting);
• A CIS summer school for trainees;
• Travel awards for trainees to attend meetings, e.g., CIS or the European Society for Immunodeficiencies (ESID);
• Visiting Scholars (medical students visit U.S. laboratories and clinics for 1 to 4 weeks; 32 Scholars in 2012), and
• Visiting professors (experts visit U.S. medical schools for 1 day of lectures and bedside rounds; 7 visits in 2012).

Non-Responsive Applications: Applications that do not include plans to maintain resources in each of these three areas - PIDDRR Registry, PIDDRR Repository, and PIDDRR Education and Training resources - will be considered non-responsive and will not proceed to peer review.

The resources maintained and developed under an award made in response to this FOA will support investigations in PIDD, represented by, but not limited to, the research encouraged through the following funding opportunity announcements:

• Small Grants on Primary Immunodeficiency Diseases (R03) (PA-10-147);
• Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21) (PAS-10-148), and
• Investigations on Primary Immunodeficiency Diseases (R01) (PAR-12-036).

The PIDDRR will assist researchers with registry, repository, and educational activities for investigations that include, but are not limited to, the following:

• Identifying the clinical, immunological, and molecular characteristics of PIDD;
• Identifying the molecular basis of PIDD;
• Advancing our understanding of how a genetic variant results in immunodeficiency;
• Discovering, developing, and improving diagnostic/newborn screening tools for PIDD;
• Discovering and/or developing new animal models for PIDD, including models appropriate to test novel clinical strategies;
• Improving understanding of existing treatments for PIDD;
• Improving understanding of complications associated with PIDD;
• Defining environmental, epigenetic, or other triggers that result in complications in individuals with PIDD; and
• Identifying and validating biomarkers for PIDD.

Resources maintained or developed under this funding opportunity are NOT intended to support the following research areas:

• Immunodeficiency resulting from infection (e.g., HIV);
• Immunodeficiency resulting from treatments (e.g., chemotherapy), exposures (e.g., radiation), or therapies (e.g., transplantation, or surgery);
• Immunodeficiency resulting from an aging or immature immune system; and
• Basic immunologic mechanisms unless directly related to understanding of primary immunodeficiency disease.

For any questions concerning clinical studies under this FOA, applicants are encouraged to contact the Scientific/Research Contact listed in Section VII. Agency Contacts.

Steering Committee

The Steering Committee will provide guidance and assistance for developing resources, including registry criteria and enrollment, repository materials, means of making resources available to the scientific community, and educational and training needs and opportunities. The Steering Committee’s membership will comprise the PD(s)/PI(s), who will serve as chair (for an award made to multiple PDs/PIs, the PDs/PIs will select one PD/PI to serve as chair), 4 to 8 other individuals from outside the grantee organization with expertise in primary immunodeficiency disease research, and the NIAID Project Scientist. Steering Committee members will be appointed (or re-appointed, in the case of renewal) after award by the PD(s)/PI(s) in consultation with the NIAID Project Scientist. The Steering Committee will hold monthly teleconferences and convene an annual face-to-face meeting in the Bethesda, Maryland area.

The Steering Committee will assist in:

• Establishing, prioritizing, and achieving the goals of, the PIDDRR;
• Periodically reviewing the PIDDRR and recommending measures to enhance content and quality, and correct deficiencies;
• Considering proposals to use the PIDDRR;
• Fostering collaborations using the PIDDRR;
• Facilitating the design and conduct of studies involving the PIDDRR;
• Periodically assessing and creating or revising as needed the PIDDRR data collection forms;
• Preparing and reviewing the agenda and material for meetings;
• Reviewing and recommending changes in research directions for NIAID approval.

Additional details about the roles and functioning of the Steering Committee are provided in Section VI.2.

Website

The PIDDRR will maintain a public website for collecting and disseminating information on itself and other areas of interest to primary immunodeficiency research, physician, and patient communities, as well as the public, including but not limited to:

• Registry content (number enrolled, disease representation, data types available);
• Repository content (cells and other materials available);
• Disease-specific criteria including information fields on enrollment forms;
• Guidance on formulating and submitting queries and a query form;
• Metrics on use of the resource; and
• Education and training opportunities.

Information should be coordinated with other resources including those in Asia (http://rapid.rcai.riken.jp/RAPID) and Europe (http://www.esid.org/).

Annual Scientific Meetings

The PD(s)/PI(s) and Steering Committee members will participate in an initial scientific meeting with the NIAID Program Scientist to be held within three months of award in the Bethesda, Maryland area, followed annually by face-to-face scientific meetings. Additional key personnel and other relevant staff may attend when appropriate. The scientific meetings will provide opportunities for members to report recent results, exchange new ideas and information, and establish collaborations. Each annual scientific meeting will serve as one of the monthly meetings of the Steering Committee.

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.
Application Types Allowed	New Renewal The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIAID intends to commit $600,000 in total costs in FY 2015 to fund a single (1) award. Future year amounts will depend on annual appropriations.
Award Budget	Application budgets are limited to $600,000 in total costs per year, including consortium F&A.
Award Project Period	Applicants may request a project period of up to five 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.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Lakshmi Ramachandra, M.Sc., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Drive, Room 3264, MSC 7616
Bethesda, MD 20892-7616
Zip Code for express couriers: 20817-7616
Telephone: 301-402-5658
Email: [email protected]

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

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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.

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

Include in the proposed budget costs for the Annual Scientific Meeting (the Steering Committee Meeting will be held jointly with the Annual Scientific Meeting), including costs for travel, lodging, and the venue. Assume that the Annual Meeting will require two days and take place in the Bethesda, Maryland area. Assume travel costs for the PD(s)/PI(s), up to five additional key personnel or other relevant staff, and all Steering Committee members for each annual meeting.

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

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

Specific Aims: List the Specific Aims of the proposed program. Describe the resources that will be provided to the research community.

Research Strategy: Provide a compelling justification for the resources proposed for development in the context of:

• needs within the research community;
• potential impact of availability and use of the information and other resources in research on primary immunodeficiency diseases; and
• ultimate potential impact on human health.

Describe the technical approaches proposed to maintain and expand the PID Research Resource (PIDDRR) Registry, Repository, and Educational and Training resources, as well as plans to develop new resources and increase the use and value of the Resource. Applicants should present their experience and any preliminary studies along with demonstrations of feasibility, pitfalls and alternative approaches. Details that should be provided include, but are not limited to the following:

• Describe the goals for resources, including the following details:
  • Enrollment in the Registry, including the numbers of individuals, representation of diseases, types of data, and approaches to attain the enrollment goals;
  • Biological samples that will be collected or developed for the Repository, including cell lines, DNA, RNA, proteins, and other biological samples; and
  • Educational and training opportunities that will be developed and provided to the community, including whether web-based media and social media will have roles.
• Describe the plans, procedures and processes to:
  • Solicit, receive, review, prioritize, and fulfill requests for resources;
  • Fulfill all regulatory agency requirements and the protection of human subjects, including confidentiality of human subjects;
  • Assess the value of the resources to the research community, including parameters to be measured;
  • Track use of the resource, including use by investigators who submit queries that are answered using the registry or obtain samples from the repository; and
  • Report annually an assessment of the content and quality of the resources, including the format of an annual report to be posted on the public PIDDRR website.

For renewals: Include a summary of the progress during the current award.

The application should also propose plans for interacting with other resources relevant to the primary immunodeficiency disease research community including:

• Center for International Blood and Marrow Transplant Research (CIBMTR),
• Primary Immune Deficiency Treatment Consortium (PIDTC), and
• Severe Chronic Neutropenia International Registry (SCNIR).

Applicants are encouraged to explore data sharing relationships with those States within the U.S. that are performing newborn screening for primary immunodeficiency diseases, consistent with applicable laws and regulations. Such data would reduce ascertainment bias by not depending on individual physician and family detection, diagnosis and reporting.

Applicants should also describe:

• Specialized facilities and equipment for supporting the registry and repository;
• Security systems and plans to safeguard privacy; and
• Systems to perform data back-up and protect / ensure data integrity.

At each re-competition, resources developed and maintained under the previous cooperative agreement are transferred to the new awardee. These resources include the registry dataset and supporting documentation, the data capture forms, computer programs for data entry, and repository samples (see http://www.usidnet.org).  Applicants must describe how these legacy resources will be managed. Provide sufficient technical detail to allow the assessment of capabilities and feasibility.

Note: The following technical details about the database are provided so that applicants can present plans for data transfer and management. The current USIDNET Registry system is built in ASP.NET/C# on the .NET 2.0 Framework with two SQL Server 2005 databases and SQL Server Reporting Services (SSRS). Data can be filtered by enrolling site, enrolling physician, disease, gender, and other criteria. Reports can be exported to XML, CSV, TIFF, PDF, web archive, or Excel. Additional information on the registry is available under the Disease Registry tab, the Registries Info link on the USIDNET home page.

Steering Committee: Describe the Steering Committee, including its composition, expertise, commitment, roles and responsibilities. Indicate sample topics that will be updated, prospective planning or executive groups, and the types of review and analysis that will be conducted to evaluate the function of the resources. If a Steering Committee is already formed, members must be identified, their roles justified, and their biosketches included in the application. Do not name the individuals unless they are already part of the applicant team or members of the current Steering Committee.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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.
• Consistent with achieving the goals of the PIDDRR, applicants are expected to include a description of methods by which information and other resources developed or maintained under this program would be provided to the research community in a timely manner, and indicate in the discussion how access to registry information and other resources would be governed.

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.

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

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

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed. Applications that do not include plans to maintain resources in each of these three areas - PIDDRR Registry, PIDDRR Repository, and PIDDRR Education and Training resources - will be considered non-responsive and will not proceed to peer review.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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? Will the project provide valuable resources, including education and training, for investigations of primary immunodeficiency diseases?

Investigator(s)

Are the PD(s)/PI(s), 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? Have the investigators demonstrated leadership in the development, maintenance and governance of research resources? Is appropriate experience described and effort proposed for the effective management of the resource? Is there experience in communication with potential users?

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? Will the resource provide valuable assistance to primary immunodeficiency disease research?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? Are appropriate approaches described for the generation, maintenance and distribution of the resources? Is a prioritization plan included for making the resource available to the broader community? Did the applicant provide sufficient detail to allow evaluation of the technical advantages and limitations of the approach and the availability of and expertise in alternative approaches?

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? Does the environment provide appropriate support for the generation, maintenance and distribution of the resources? Are the specialized facilities and equipment, security systems, and systems to ensure data integrity adequate?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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) Genome Wide Association Studies (GWAS) Additionally, reviewers will comment on the adequacy of plans to provide resources to the research community in a timely manner, and suitability of plans for accessing registry information and governance of other 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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIAID, 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 Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

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

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

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

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

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Planning, defining, directing the research plan and goals, including
  • overseeing the execution of the program as a whole;
  • performing the scientific activities of the research plan; and
  • administratively managing the cooperative agreement.

In addition, the PD(s)/PI(s) of the PIDDRR will:

• participate in all Steering Committee activities;
• be a voting member of the Steering Committee;
• serve as the Chair of the Steering Committee (for an award having multiple PD(s)/PI(s), the PD(s)/PI(s) will select one PD/PI from amongst themselves to serve as Chair of the Steering Committee);
• accept the close cooperation and participation of the Steering Committee in the relevant aspects of scientific and technical management of the project;
• ensure compliance of the PIDDRR with all appropriate regulations, including protection of human subjects, patient privacy, and the assurance program of the Federal Office of Human Research Protection (OHRP); (NIH policy requires that clinical studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf);
• ensure that the PIDDRR establishes and implements mechanisms of quality control in data collection and management;
• seek opportunities for collaborations with other investigators outside of the PIDDRR in order to enhance and extend the value of the PIDDRR database;
• cooperate with the NIH staff members in the periodic evaluation of the Program and its specific aspects; and
• commit to making the resources developed under this program available to the broad research community.

The responsibilities of the PD(s)/PI(s) also include:

• Maintaining a resource available to the community for research in primary immunodeficiency in the areas identified in this FOA;
• Optimizing and enhancing the quality and value of the resources in aspects relevant to the NIAID; and
• Participating in new research and analyses using the PIDDRR data in areas relevant to the priorities of the NIAID as stated in this FOA, including efforts to ensure timely publication of such studies in peer reviewed biomedical journals. Although initiating new research and analyses is not the main role of the PIDDRR, investigators involved in PIDDRR are expected and encouraged to actively engage in such efforts.

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

The responsibilities of NIH staff members will include, but will not be limited to, the following activities:

• Monitoring PIDDRR progress and, when appropriate, coordinating external reviews;
• Serving as a resource with respect to other ongoing NIAID and NIH activities that may be relevant to the PIDDRR efforts;
• Reviewing mechanisms for data collection, analysis and review, when appropriate; and
• Reviewing Progress: Performance of the PIDDRR will be reviewed as requested by the NIAID, in addition to the annual progress report. For example, the NIH Project Scientist will review mechanisms established by PIDDRR for data collection, management and analysis, when appropriate. Also evaluated will be the assistance the PIDRR provides that results in publications in peer-reviewed science journals.

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NIH Project Scientist will:

• Participate as a voting member of the PIDDRR Steering Committee;
• Help coordinate program activities through the PIDDRR Steering Committee;
• Participate in the design of activities recommended by the PIDDRR Steering Committee.
• Assist awardees in refining and implementing the Resource Sharing Plan with respect to providing resources to the research community in a timely manner, ensuring access to registry information, and appropriate governance of other resources;
• Advise in the selection of sources or resources (e.g., determining where a particular resource may be found);
• Assist in promoting and encouraging the sharing of unique research resources developed under this program;
• Advise in management and technical issues and performance; and
• Help to maintain the overall scientific balance on the program commensurate with emerging research opportunities.

Additionally, an agency program official 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:

Within two months of award a Steering Committee will be established by the PD(s)/PI(s). The Steering Committee will serve as the main governing board of the PIDDRR. The PD(s)/PI(s) will be required to accept and implement policies approved by the Steering Committee and the NIAID. The responsibilities of the Steering Committee include:

• Prepare and review the Agenda for PIDDRR meetings (Annual Scientific Meeting and all face-to-face and teleconference Steering Committee meetings);
• Establish priorities for scientific studies;
• Consider proposals to use the PIDDRR for studies pertinent to specific PID subject area(s);
• Facilitate the design and conduct of studies relevant to specific PID subject area(s) and involving PIDDRR resources;
• Periodically assess and revise relevant sections of the PIDDRR data collection forms;
• Foster collaborations among members of the PIDD research community;
• Periodically review the PIDDRR and recommend measures to enhance content and quality, and to correct deficiencies;
• Provide advice on research direction and problems encountered during the award project period;
• Recommend methods for distribution of resources to the research community; and
• Review and recommend changes in research directions for NIAID approval;

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 arbitration. An Arbitration 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 arbitration procedure in no way affects 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.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: [email protected]

David R. Johnson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-591-0907
Email: [email protected]

Lakshmi Ramachandra, M.Sc., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-5658
Email: [email protected]

Shellie Wilburn
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-594-9676
Email: [email protected]

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 Parts 74 and 92.