Part I Overview Information

---

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID) (http://www.niaid.nih.gov)

Title: Resources to Assist Investigations in Primary Immunodeficiency Diseases (U24)

Announcement Type
New

Update: The following update relating to this announcement has been issued:

• December 11, 2013 - This RFA has been reissued as RFA-AI-13-054.

Request For Applications (RFA) Number: RFA-AI-08-066

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.856

Key Dates
Release Date: January 12, 2009
Letters of Intent Receipt Date: March 13, 2009
Application Receipt Date: April 14, 2009
Peer Review Date: June, 2009
Council Review Date: October, 2009
Earliest Anticipated Start Date: January, 2010
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/
Expiration Date: April 15, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Allergy and Infectious Diseases (NIAID), the National Institutes of Health (NIH), invites applications from institutions or organizations for continued maintenance and development of resources to support research on primary immunodeficiency diseases. These resources fall into the following broad categories;
  • A registry of individuals with primary immunodeficiency disease;
  • A repository of reagents and other materials to aid primary immunodeficiency disease research;
  • Educational resources to provide training, disseminate information, and encourage collaborative research on primary immunodeficiency disease.
  • A Steering Committee will be formed after award to assist the applicant in these activities.
• Mechanism of Support. This FOA will utilize the Resource-Related Research Projects Cooperative Agreement (U24) grant mechanism.
• Funds Available and Anticipated Number of Awards. It is anticipated that $600,000 TOTAL COSTS will be available in FY 2010 to support this program and that one (1) award will be made. An award issued under this FOA is contingent upon the availability of funds and the submission of a meritorious application.
• Budget and Project Period. The total project period for an application submitted in response to this FOA is five (5) years. Total costs are limited to $600,000.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. Applicants may not submit more than one application.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are not permitted in response to this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

---

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

---

Section I. Funding Opportunity Description

---

1. Research Objectives

Background

Primary immunodeficiency diseases result from inherited defects in the immune system. More than 150 primary immunodeficiency diseases and 120 different genes causing these diseases have been identified. While individual primary immunodeficiency diseases are rare, as a group they may affect 1-2% of the population of the United States. Understanding the genetic and mechanistic basis of primary immunodeficiency diseases provides unique insight in to the functioning of the immune system. In addition to the benefits to affected individuals, this information furthers all immunological research.

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 (USIDNET) <http://www.usidnet.org >. One of the purposes of this contract was to maintain and develop resources for primary immunodeficiency disease research. These resources included a registry of patients, a repository of cell lines, and educational and training opportunities.

The USIDnet contract also included funds for pilot research projects. Those activities have been continued through separate funding opportunities. See PAR-07-446, Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21), and PAR-07-447, Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R03).

USIDnet Registry Activities

The primary immunodeficiency disease registry was initially established in 1993 with NIAID support and focused on individuals with chronic granulomatous disease. Since that time the registry has expanded to include information on individuals with X-linked agammaglobulinemia, hyper-IgM syndrome, severe combined immunodeficiency disease, common variable immunodeficiency, Wiskott-Aldrich syndrome, DiGeorge syndrome, and leukocyte adhesion deficiency. The registry currently has information on approximately 2000 individuals. Information for inclusion in the registry is submitted by primary immunodeficiency diseases researchers via paper forms or through a secured web-based system. Researchers have used registry information to investigate specific questions or to identify physicians who are caring for individuals with specific characteristics. Information on the USIDnet registry is available at <http://www.usidnet.org/pages/Registry.jsp>.

USIDnet Repository Activities

The USIDnet repository currently has 36 cell lines available from individuals with a variety of primary immunodeficiency diseases. <http://ccr.coriell.org/Sections/Collections/USIDNET/?SsId=15> Additional cell lines from individuals with primary immunodeficiency diseases are available in other collections housed at Coriell Institute, for example, the NIGMS Human Genetic Cell Repository.

USIDnet Educational and Training Activities

USIDnet has provided partial support for an annual scientific conference typically held in conjunction with the Federation of Clinical Immunology Societies (FoCIS) annual meeting (see http://www.clinimmsoc.org/meetings/2008/pid08/), a summer school for trainees (see http://www.clinimmsoc.org/meetings/2008/pid08_school/), and travel awards to attend meetings of the European Society for Immunodeficiencies. Support has also been provided for short-term training and visiting professors.

Research Objectives and Scope

The primary objective of this FOA is to continue support for continued maintenance of resources provided by the USIDnet Registry, USIDnet Repository, and USIDnet Educational and Training activities and to expand these activities as well as to provide for the development of reagents and other materials to support research on primary immunodeficiency diseases. These resources fall into the three broad categories:

• Registry- Maintain the current registry of PID individuals, enroll new individuals in the registry, expand the types of data collected, and increase collaboration with other registries with an interest in primary immunodeficiency disease . The collection of human data associated with a clinical trial is within the scope of the FOA, however, this FOA does not support clinical trials.
• Repository- Maintain the current repository of cell lines, add additional cell lines as appropriate, and expand repository activities to include development of reagents and other materials which are difficult for the research community to obtain.
• Education and Training- Provide training and educational opportunities, disseminate information, and encourage collaborative research on primary immunodeficiency disease.

Applications not including plans to develop resources in each of these three areas, will not be considered responsive, and will not be reviewed.

The resources developed under this award should support the types of research solicited through the following funding opportunity announcements PAR-07-446, Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R21); PAR-07-447, Exploratory/Developmental Investigations on Primary Immunodeficiency Diseases (R03); and PAR-08-206, Investigations on Primary Immunodeficiency Diseases (R01). For example, the resources should support research projects not limited to:

• Identifying the clinical, immunological, and molecular characteristics of genetically determined primary immunodeficiency diseases, including disorders in which immunodeficiency is associated with hepatic, enteric, and other organ dysfunction;
• Identifying the molecular basis of primary immunodeficiency diseases, including disorders in which immunodeficiency results from abnormalities in hematopoietic stem cell development;
• Advancing our understanding of how a genetic variant results in immunodeficiency;
• Discovering/developing improved diagnostic/newborn screening tools for primary immunodeficiency diseases;
• Discovering/developing new animal models for primary immunodeficiency diseases, including models appropriate to test novel clinical strategies;
• Improving and better understanding of existing treatments for primary immunodeficiency diseases;
• Understanding complications associated with primary immunodeficiency diseases;
• Defining environmental, epigenetic, or other triggers that result in complications in individuals with primary immunodeficiency diseases; and
• Identifying and validating biomarkers for primary immunodeficiency diseases.

Resources maintained or developed under this funding opportunity are NOT specifically 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.

Resources maintained or developed under this funding opportunity may be used to support clinical trials and epidemiologic studies by serving as the data coordinating center, data repository, and/or sample repository if the data and/or samples will be made available to all investigators not just those participating in the clinical trial.

Plans to address all regulatory agency requirements and the protection of human subjects must be described in the application. For any questions concerning clinical studies under this FOA, applicants are encouraged to contact the Program staff listed in Section VII Agency Contacts.

Steering Committee

Project Directors/Principal Investigators (PDs/PIs) funded under this program will form a Steering Committee after award. This steering committee will provide recommendations on resource development, on methods for making resources available to the scientific community, and on educational and training needs and opportunities. The steering committee will also assist in fostering collaborations among the members of the primary immunodeficiency research community. The Steering Committee will be comprised of the awardee PD/PI, who will serve as chair, the Project Scientist and 4-6 other individuals with expertise in primary immunodeficiency disease research. Steering Committee members will be selected after award by the PD/PI in consultation with the Project Scientist. The steering committee will conduct teleconferences on a quarterly schedule and will participate in an annual face-to-face meeting to discuss progress and future plans.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

---

1. Mechanism of Support

This funding opportunity will use the Resource-Related Research Projects Cooperative Agreement (U24) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

Plans beyond the current funding opportunity are indefinite.

2. Funds Available

The estimated amount of funds available for support of one project awarded as a result of this announcement is $600,000 TOTAL COSTSfor fiscal year 2010. Future year amounts will depend on annual appropriations. An applicant may request a project period of up to five years.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• 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
• 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)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewal applications are not permitted in response to this FOA.

Applicants may not submit more than one application.

Applications not including a Sharing Unique Resources Plan will not be considered responsive and will not be reviewed.

Section IV. Application and Submission Information

---

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Foreign Organizations (Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

• Request budgets in U.S. dollars.
• Contain detailed budgets. See NOT-OD-06-096.

In addition, for applications from foreign organizations:

• Charge back of customs and import fees is not allowed.
• Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
• Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: March 13, 2009
Application Receipt Date: April 14, 2009
Peer Review Date: June, 2009
Council Review Date: October, 2009
Earliest Anticipated Start Date: January, 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone: 301-496-8426
Fax: 301-480-2408
Email: PJackson@niaid.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Peter Jackson, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone: 301-496-8426
Fax: 301-480-2408
Email: PJackson@niaid.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Annual Scientific/Steering Committee Meetings

Travel costs to attend an Annual Scientific/Steering Committee Meeting must be included in the budget request. Assume that the Annual Meeting will require two days and take place in the Bethesda, Maryland area. Travel costs for the PD/PI, up to five additional key personnel, and all Steering Committee members should be requested for each annual meeting.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

Preparing Applications under this Funding Opportunity Announcement

Because of the highly focused and practical nature of this FOA, certain aspects of the PHS 398 Research Plan should be especially well developed:

Background and Significance

Include within the Background and Significance section a well developed justification for the choice of resources proposed for development in the context of: a compelling need within the research community; the potential impact of use of the information and other resources in research on primary immunodeficiency diseases; and its ultimate potential impact on human health.

Research Design and Methods

Include within the Research Design and Methods section (as part of the 25 page limitation items 2-5) a description of the technical approaches proposed to maintain and expand the USIDnet Registry, USIDnet Repository, and USIDnet Educational and Training activities as well as develop new resources in sufficient detail to allow ready evaluation of: the appropriateness of the approach; the technical advantages and limitations of the approach; the availability of and expertise in alternative approaches; and the overall feasibility of generating useful resources that can be distributed to and used by the broader scientific research community. Also include a description of goals including numbers of individuals to be enrolled in the registry, or for expansion the number and types of samples which will be collected for the repository. The application should also propose plans for interacting with other NIH-funded resources with relevance to the primary immunodeficiency disease research community such as the International Bone Marrow Transplant Registry, and the Severe Chronic Neutropenia International Registry. Applications should include a discussion of plans to harmonize database structures and data elements to improve the ability to combine information from different datasets for analysis. In addition a discussion of the specialized facilities and equipment for supporting the registry and repository including the security systems and plans which will be used to safe-guard privacy should be included.

Resources developed under the USIDnet contract will be transferred to the awardee. (See http://www.usidnet.org.) These include the registry dataset and supporting documentation, the data capture forms, computer programs for data entry, and repository samples. The application should describe how these resources will be managed.

Potential members of the steering committee should NOT be identified in the application. The application should identify the types of expertise which will be represented in the steering committee.

Annual Scientific/Steering Committee Meetings

Awardees must agree to the Cooperative Agreement Terms and Conditions of Award described in Section VI.2.A Award Administration Information regarding mandatory participation in the Steering Committee.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

Sharing Unique Resources Plan

Separate from and in addition to the Resource Sharing Plan(s) described below, a Sharing Unique Resources Plan must be included, which details a description of the methods by which information and other resources developed or maintained under this program will be provided to the research community in a timely manner. The Plan description is limited to five pages and should be included at the beginning of the Resource Sharing Section (Section K). Entitle this part Sharing Unique Resources Plan. The plan should also include a discussion of how access to registry information and other resources will be governed. Budgetary items to cover anticipated costs for associated with the sharing plan should be included in the regular Budget and Budget Justification Sections of the application.

Applications not including a Sharing Unique Resources Plan will not be considered responsive and will not be reviewed.

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

Section V. Application Review Information

---

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIAID and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• 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 a priority score.
• Receive a written critique.
• 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 peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• Adequacy of plans to make resources available in a rapid manner to the scientific research community

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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 resources developed to support research on primary immunodeficiency diseases be of broad benefit to the scientific community?
Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, 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? Does the application include all the expertise needed for resource development and management? Are the administrative plans for the management of the projects appropriate, including plans for resolving conflicts?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion 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? Are there adequate and appropriate computer resources to support the proposed registry activities including computer security measures? Are there adequate and appropriate facilities to support the proposed repository activities?

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, 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.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

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.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

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.

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

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

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).

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

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 (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Sharing Unique Resources Plan: For this FOA, the Sharing Unique Resources Plan will be considered and commented on by the Peer Review Group, but will not be used in determining scientific merit and priority score. After award, the Plan may be re-negotiated with the NIH Project Scientist.

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

---

1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See Also Section IV.5. Funding Restrictions.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. 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.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining the research plan and goals; overseeing/performing the scientific activities of the research plan; cooperating with NIAID programmatic, technical, and administrative staff; and administratively managing the U24 grant. Each PD/PI will be a voting member of the Steering Committee, will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee. The PD/PI must agree to accept the close cooperation and participation of the Steering Committee in the relevant aspects of scientific and technical management of the project. The PD/PI must also be committed to making the resources developed under this program available to the broader research community, subject to the rights described below.

Monitoring Clinical Studies

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.

Intellectual Property

The NIAID recognizes that intellectual property rights are likely to play an important role in achieving the goals of this program. To this end, all awardees understand and acknowledge the following:

• The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
• Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
• The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 200-212 (Bayh-Dole Act) and 37 CFR 401.

Awardees are encouraged to reach early consensus with any proposed partners regarding intellectual property and other legal matters that may arise during the project. In addition, awardees are expected to exercise their Bayh-Dole rights in a manner that does not conflict with the goals of this award or the intent of the Bayh-Dole act to promote the utilization, commercialization, and availability of U.S. Government-funded inventions for public benefit. Awardees are expected to make new resources known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms; and to make the resources available through appropriate channels.

Publications

The PD/PI will be responsible for the timely submission of all abstracts, manuscripts, and reviews (co)authored by members of the grant and supported in part or in total under this Agreement. Publications or oral presentations of work performed under this Agreement are the responsibility of the PD/PI and will require appropriate acknowledgement of NIAID support. Timely publication of major findings is encouraged.

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.

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

A program official from the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) will serve as the NIH Project Scientist for this program, facilitating but not directing activities. In conjunction with other NIAID scientific program staff, and the Steering Committee, the NIH Project Scientist will: assist awardees in refining and implementing the Sharing Unique Resources Plan after award; provide advice and guidance on technical issues; participate in the design of activities recommended by the Steering Committee; advise in the selection of sources or resources (e.g., determining where a particular resource may be found); or advise in management or technical performance. The NIH Project Scientist will help to maintain the overall scientific balance on the program commensurate with emerging research opportunities, and will participate as a voting member of the Steering Committee. The NIH Project Scientist will also: help coordinate program activities through the Steering Committee; and assist in promoting and encouraging the sharing of unique research resources developed under this program. The NIH Project Scientist will schedule the meetings of the Steering Committee.

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.

2.A.3. Collaborative Responsibilities

PDs/PIs funded under this program will form a Steering Committee after award to:

• foster collaborations among the Primary Immunodeficiency Disease Community;
• facilitate access to resources from other NIAID programs;
• provide advice on research direction and problems encountered during the funding period;
• discuss and recommend methods for distribution of resources to the broader scientific community; and
• review and recommend changes in research directions for NIAID approval.

Each PD/PI will be a voting member of the Steering Committee and one PD/PI shall serve as the Steering Committee Chair. The Steering Committee will confer by teleconference on a quarterly schedule and will participate in an annual face-to-face meeting in the Bethesda, MD area to discuss results and research plans. The annual Steering Committee meetings will be held in conjunction with the Annual Scientific Meetings (see below). Each full member will have one vote. In order for a decision or course of action to be recommended by the Steering Committee, a majority of the possible votes must be cast in favor of the decision or course of action. The awardee will be required to accept and implement policies approved by the Steering Committee.

NIAID intends to support the peer-reviewed studies proposed in the awarded grant application. However, under special circumstances, the Steering Committee will establish guidelines and review procedures to evaluate and determine opportunities for redirection or modification of the peer-reviewed projects. Such recommendations may be initiated by advice from an individual PD/PI, a member of the Steering Committee, or from NIAID staff. All recommended changes must be reviewed and approved by the NIAID program official prior to implementation and redirection of funds.

Annual Scientific Meetings

The awardee will participate in an initial scientific meeting, arranged by the NIH Project Scientist, to be held soon after award in the Bethesda, Maryland area. The meeting will also be attended by members of the Steering Committee. The awardee will also participate in face-to-face scientific meetings of all PDs/PIs to be held annually thereafter. All PDs/PIs are required to attend these meetings, and may include additional staff from their grant when appropriate. The scientific meetings will be open to members of the NIH extramural staff and invited guests, and will provide opportunities for members to report recent results, exchange new ideas and information, and establish collaborations. This meeting will serve as one of the quarterly meetings of the Steering Committee.

2.A.4. Arbitration Process

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.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

---

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Josiah Wedgwood M.D., Ph.D.
Division of Allergy, Immunology & Transplantation
National Institute of Allergy and Infectious Diseases
Room 3019, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-7104
FAX: (301) 480-1450
Email: Jwedgwood@niaid.nih.gov

2. Peer Review Contacts:

Peter Jackson Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3133, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Phone: 301-496-8426
Fax: 301-480-2408
Email: PJackson@niaid.nih.gov

3. Financial or Grants Management Contacts:

Terri Jarosik
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2117, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 451-9892
Fax: (301) 493-0597
Email: tjarosik@niaid.nih.gov

Section VIII. Other Information

---

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.