Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov/)
The Juvenile Diabetes Research Foundation International (JDRFI), (http://www.jdf.org/)

Components of Participating Organizations
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www.niddk.nih.gov/)
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov/ )
The Juvenile Diabetes Research Foundation International (JDRFI), (http://www.jdf.org/)

Title: Cooperative Study Group for Autoimmune Disease Prevention

Announcement Type
This is a reissuance with modifications of RFA-AI-00-016, which was previously released on September 7, 2000.

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

• June 17, 2011 - This RFA has been reissued as RFA-AI-11-034.

Request For Applications (RFA) Number: RFA-AI-05-026

Catalog of Federal Domestic Assistance Number(s)
93.855, 93.847, 93.865, 93.113

Key Dates
Release Date: May 12, 2005
Letters of Intent Receipt Date(s): September 12, 2005
Application Receipt Dates(s): October 12, 2005
Peer Review Date(s): February, 2006
Council Review Date(s): May, 2006
Earliest Anticipated Start Date: July, 2006
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/rfa-05-026.htm
Expiration Date: October 13, 2005

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Single institutions or consortia of institutions are invited to participate in a cooperative research group focusing on prevention of human autoimmune diseases, with an emphasis on type 1 diabetes. In FY 2006, the co-sponsoring NIH Institutes and the Juvenile Diabetes Research Foundation International (JDRFI) anticipate awarding a total of $4.5 million to fund four to six awards, using the single-project (U01) and multi-project (U19) cooperative agreement award mechanisms. Additional discretionary funds of approximately $2.5 million will be allocated to the Study Group to fund innovative collaborative, discovery-based, and/or pilot and feasibility projects consistent with the overall goal of autoimmune disease prevention. Eligible institutions include for-profit or non-profit organizations; public or private institutions, such as universities, colleges, hospitals, and laboratories; units of State and local governments; or eligible agencies of the Federal government. Foreign institutions are not eligible to apply as the primary applicant institution in a multi-project application, but may submit a single-project application or enter into a consortium with a domestic institution as the primary applicant. This RFA will not support clinical trials or studies of global immunosuppressive therapies, and proposals for clinical trials may not be submitted in the initial application. Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his or her institution to develop an application as the Principal Investigator. A Principal Investigator may submit only one application. However, participation of a Principal Investigator as a project leader in multi-project applications (U19 mechanism) is allowed if there is no scientific overlap with the application submitted by the Principal Investigator. Applications must be prepared using the most current PHS 398 research grant application instructions and forms, available at http://grants.nih.gov/grants/funding/phs398/phs398.html. For further assistance contact GrantsInfo, telephone (301) 710-0267, email: GrantsInfo@nih.gov. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

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 and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
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

1. Research Objectives

The National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development (NICHD), the National Institute of Environmental Health Sciences (NIEHS), and the Juvenile Diabetes Research Foundation International (JDRFI) invite applications from single institutions or consortia of institutions to participate in the Cooperative Study Group for Autoimmune Disease Prevention (CSGADP), hereinafter referred to as the Study Group . The CSGADP is a unique multi-center cooperative program established in 2001 as a collaborative network of investigators, with a focus on autoimmune disease prevention and an emphasis on type 1 diabetes. The current Study Group has as its foundation a set of single- and multi-project (U01 and U19) cooperative agreements coordinated by a Steering Committee. It also draws upon additional discretionary funds to support a range of innovative collaborative projects and pilot and feasibility projects conducted within and outside the Study Group membership to further the goals of the CSGADP program. These goals include understanding the immune mechanisms that underlie autoimmunity and autoimmune disease, and the mechanisms and consequences of manipulation of the immune response in autoimmunity, as well as applying this information to the prevention of autoimmune diseases in humans. The purpose of this RFA is to continue support for the CSGADP program by awarding new and competing continuation grants. The long-term goal of this program is to develop the knowledge base necessary to design interventions for the prevention of autoimmune disease that could be administered efficiently and safely to individuals at risk or to the general population, including infants and children. While such interventions might also be useful in established disease, the focus of this program is on prevention rather than therapy. For the purpose of this RFA, prevention of autoimmune disease is defined as halting the development of an autoimmune disease prior to clinical onset by means other than global immunosuppression.

Background

Autoimmune diseases are debilitating, chronic illnesses that affect multiple organ systems and disproportionately afflict women. Type 1 diabetes afflicts over 600,000 persons in the United States with peak onset in childhood. Although insulin treatment is available, long-term complications include kidney failure, blindness, amputations, and accelerated cardiovascular disease. Patients with type 1 diabetes are also at higher risk of developing celiac disease, another autoimmune condition that causes inflammation of the digestive tract. Multiple sclerosis afflicts over 350,000 persons in the United States; women are affected twice as frequently as men. Although the course of the disease is unpredictable, central and peripheral nerve impairment resulting from multiple sclerosis can lead to blindness, weakness, loss of bowel and bladder control, and confinement to a wheelchair. Rheumatoid arthritis, which also affects primarily women, causes chronic pain, crippling deformity, and loss of independence. This disease afflicts over 2 million individuals in the U.S. population. Systemic lupus erythematosus is a multi-system autoimmune disease that disproportionately affects African-American women and accounts for over 100,000 hospitalizations each year. Sj gren's syndrome, which affects predominantly middle-aged women, results in diminished lacrimal and salivary gland function. Patients may suffer dysphagia, atrophic gastritis, esophageal mucosal atrophy, constipation, and sub-clinical pancreatic insufficiency. About 30% of patients with rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis suffer secondary Sj gren's syndrome, while 2 to 5% of people aged 60 and above have primary Sj gren's syndrome.

The 1999 Institute of Medicine report, Vaccines for the 21st Century: A Tool for Decision Making (http://www.iom.edu/report.asp?id=5648) concluded that the development of vaccines to treat or prevent type 1 diabetes, multiple sclerosis, and rheumatoid arthritis would bring exceptionally high economic and health benefits. Preventive vaccines for other autoimmune diseases, including the less common but devastating pediatric autoimmune diseases such as juvenile rheumatoid arthritis and Kawasaki's disease, would also enhance public health. The Congressionally established Diabetes Research Working Group's 1999 report entitled Conquering Diabetes: A Strategic Plan for the 21st Century (http://www.niddk.nih.gov/federal/dwg/fr.pdf) highlighted basic and clinical research into the pathogenesis and prevention of type 1 diabetes as an extraordinary opportunity to significantly improve the future health of the nation. The January 2002 Autoimmune Diseases Research Plan (http://www.niaid.nih.gov/dait/pdf/ADCC_Report.pdf), formulated by the Autoimmune Disease Coordinating Committee under the auspices of the NIH, similarly emphasized the importance and great potential benefit of research efforts aimed at prevention of autoimmune diseases, including the development of new knowledge about underlying mechanisms of autoimmune diseases, identification and development of biomarkers, and identification of at-risk individuals.

Recent evidence suggests that autoimmunity or the autoimmune process may precede by years the development of clinical disease in type 1 diabetes and other autoimmune diseases. Although loss of beta cell function with development of hyperglycemia defines the diagnosis of type 1 diabetes, evidence of autoimmunity manifested by multiple autoantibodies to islet antigens may be detectable years earlier. In addition, evidence of autoimmunity in healthy individuals (e.g., multiple autoantibodies in family members of patients with type 1 diabetes who do not develop disease, e.g., non-progressors) suggests that mechanisms to control autoimmunity may be operative in immune homeostasis in healthy individuals. Similarly, synovial cell activation and inflammation in rheumatoid arthritis may precede the onset of multiarticular pain and cartilage destruction, the hallmarks of this disease. Increased understanding of the processes for containment of autoimmunity found in healthy individuals, novel strategies to control or prevent autoimmunity prior to the onset of clinical disease, and safe and rational application of these strategies to humans are needed.

Since the onset of the autoimmune process may precede by years the diagnosis of disease, a further understanding of neonatal and pediatric immune homeostasis is needed, both in healthy and autoimmune prone individuals. Intervention at the earliest possible stage may be optimal for preventing these diseases.

Type 1 diabetes and other autoimmune diseases have been prevented in animal models using a variety of agents, hypothesized to be acting as toleragens or immunomodulators. However, our understanding of the mechanism and consequences of these approaches in animals is incomplete. Likewise, information on immune homeostasis of autoimmune responses in humans is lacking. Nevertheless, the ability to selectively prevent development of, or control the activity of, autoreactive cells prior to onset of clinical disease without impairing protective immune responses appears feasible.

Research Objectives and Scope

This RFA will support a Cooperative Study Group focused on research for the prevention of human autoimmune disease. For the purpose of this RFA, prevention of autoimmune disease is defined as halting the development of an autoimmune disease prior to clinical onset by mechanisms other than global immunosuppression. The ultimate goal of this research is to develop the knowledge base necessary to design preventive interventions that could be administered efficiently and safely to at-risk individuals or to the general population, including infants and children. While the interventions may also be beneficial in established disease, the focus of this RFA is on prevention rather than therapy. Clinical studies are strongly encouraged. Animal studies proposed under this RFA must document the relevance of the model to the development of preventive strategies for human autoimmune diseases. Multi-project applications must include at least one project focused directly on type 1 diabetes. Applications that include projects on other autoimmune diseases or projects related to more than one autoimmune disease are particularly encouraged; however, applications may focus entirely on diabetes.

Research projects must contribute knowledge critical to achieving both of the following goals:

1. Advance the understanding of immune homeostasis in autoimmune diseased states as well as non-diseased states. This area includes studies of the immune control of autoantigen-specific T or B cells by mechanisms including peripheral deletion, anergy, or control by other protective cells, as well as research on the dysregulation of immune homeostatic mechanisms in autoimmune diseases. Research topics include, but are not limited to, the following:

• Delineation of the phenotype and function of regulatory and effector T cell populations in target tissues and associated lymphoid organs;
• Development and regulation of the immune response to self in healthy and autoimmune prone infants and children;
• Definition of the role of the innate immune system in the maintenance and breakdown of immune homeostasis;
• Determination of the function of antigen processing and antigen presenting cell activity in the development and maintenance of self tolerance; and
• Definition of the role of genetic susceptibility and environmental influences on loss of homeostasis in autoimmune disease.

2. Design and develop interventions to prevent human autoimmune diseases, with special emphasis on type 1 diabetes. This includes the application of new information on the autoimmune disease process to facilitate the design of novel approaches and the improvement of promising strategies for autoimmune disease prevention. Research may include studies of the feasibility and mechanisms of preventive approaches in humans. Research topics include, but are not limited to, the following:

• Practical approaches to target agents to desired cellular populations and to evaluate their effectiveness in vivo;
• Identification and testing of new adjuvants and delivery approaches to boost regulatory cells and other regulatory mechanisms;
• Analyses of the consequences of intervention approaches on protective immunity and autoimmune responses;
• Development of practical means to identify populations most likely to benefit from specific interventions;
• Identification, development and validation of biomarkers of disease risk, stage, activity, and immune responses; and
• Development and application of clinically relevant animal models to facilitate the translation of preventive approaches from animals to humans.

Studies of vaccines or therapeutics directed against infectious agents may be included if there is strong evidence for a causal relationship between the infectious agent and the occurrence of an autoimmune disease in the infected population.

Applicants are strongly encouraged to include studies involving human subjects and human materials as an integral part of research projects. Examples of clinical studies that may be proposed include: immunological studies of patient samples obtained from ongoing or completed clinical trials, development or validation of biomarkers of disease risk, and comparative analyses of immune responses in diseased and non-diseased individuals. This RFA will not support clinical trials. Support for clinical trials resulting from research conducted by the Study Group may be sought through arrangements with other established clinical research programs, including but not limited to the Autoimmunity Centers of Excellence, the Immune Tolerance Network (http://www.immunetolerance.org/) and the Diabetes Prevention Trial-Type 1/Diabetes TrialNet (http://www.diabetestrialnet.org/en/index.html).

Specifically excluded from the scope of this RFA are studies of globally immunosuppressive therapies. This is in keeping with the above definition of prevention of autoimmune disease which, for the purpose of this RFA, specifically excludes global (general or non-antigen specific) immunosuppression as a means of halting the development of autoimmune disease.

A Steering Committee will serve as the governing body of the Study Group and will be responsible for the development and implementation of the Study Group Plan (see Section VI.2.A.3 below). At a minimum, the Steering Committee will be composed of the Principal Investigators of each of the awarded grants and the NIH Scientific Coordinator serving as a representative of the cosponsors. The Steering Committee or the NIH may identify and appoint other members, as appropriate. Each member of the Steering Committee shall have one vote. A Chairperson will be selected by the Steering Committee from among the non-federal Committee members. Subcommittees of the Steering Committee may be established as necessary. The Steering Committee will meet at least twice in the first year and at least annually thereafter. The NIAID Scientific Coordinator will schedule the meetings of the Steering Committee and actively assist the Chairperson in developing the meeting agendas. Each Steering Committee member will be expected to participate in all meetings and other Steering Committee activities, such as conference calls and subcommittee meetings, as may be necessary to accomplish the work of the Study Group.

Discretionary Fund

To complement the individual projects from each application, the Study Group will have access to a discretionary fund that may be used to support various innovative projects and research resources including, but not limited to, the following:

Innovative Projects

• Pilot and feasibility studies designed to gather preliminary results in support of new grant applications focused on autoimmune disease prevention;
• Hypothesis-driven studies of limited scope designed to complement or augment existing projects within the Study Group; and
• Discovery-based studies designed to enable and/or stimulate hypothesis-driven research in autoimmune disease prevention.

Research Resources

• Development and validation of novel reagents or animal models valuable for autoimmune disease prevention research; and
• Modification or expansion of approved cores, or establishment of new cores, to serve the autoimmune disease prevention research projects of the Cooperative Study Group.

The Study Group Steering Committee will be responsible for establishing procedures for the solicitation, review and approval of projects to be supported by the discretionary fund.

JDRFI Co-sponsorship

These applications may be co-funded by JDRFI; consequently, applicants are hereby notified that a submission of an application to this announcement constitutes an agreement on the part of the applicant to allow NIAID to share applications and summary statements with JDRFI.

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

1. Mechanism(s) of Support

This funding opportunity will use the NIH single project cooperative agreement (U01) and multi-project cooperative agreement (U19) award mechanisms.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The NIH U01/U19 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator 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".

At this time, the NIAID has not determined whether or how this solicitation will be continued beyond the present RFA. The total project period for applications submitted in response to this RFA may not exceed five years.

2. Funds Available

The participating ICs NIAID, NIDDK, NICHD, NIEHS and the JDRFI intend to commit approximately $4.5 million in FY 2006 to fund approximately four to six new and/or competing continuation grants in response to this RFA. Although it is the intent of the cosponsors to devote at least half of the available funds to support multi-project (U19) awards, the distribution of available funds between single-project (U01) and multi-project (U19) awards is contingent upon receipt of a sufficient number of meritorious applications of each type. In addition to these awards, it is anticipated that additional discretionary funds, approximately $2.5 million per year, will be made available to support additional projects as described under Research Objectives and Scope above.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size of each award will also vary. In previous years of this program, the average amount of funding has ranged from $600,000 to $800,000 annual direct costs for U19 grants and from $100,000 to $250,000 annual direct costs for U01 grants. In the interest of Study Group cohesion, applicants should request and plan for a project period of five years. 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. 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.

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

• For-profit organizations
• Non-profit organizations
• Public or private institutions, such as universities, colleges, hospitals, and laboratories
• Units of State government
• Units of local government
• Eligible agencies of the Federal government
• Foreign Institutions
• Domestic Institutions

Foreign institutions are not eligible to apply as the primary institution on a multi-project (U19) application, but may enter into a consortium or subcontract with a domestic institution as the primary applicant. Foreign institutions are eligible to submit single-project (U01) applications.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their 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 programs.

2. Cost Sharing or Matching

Not applicable

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria
Not applicable

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 on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

• Charge back of customs and import fees is not allowed.
• Format: every effort should be made to comply with the format specifications, which are based upon a standard US paper size of 8.5" x 11."
• Funds for up to 8% administrative costs (excluding equipment) can now be requested (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-028.html)
• 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 Requirements, "Cooperative Agreement Terms and Conditions of Award".

Proposed research should provide a unique research opportunity not available in the U.S.

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(s): September 12, 2005
Application Receipt Dates(s): October 12, 2005
Peer Review Date(s): February, 2006
Council Review Date(s): May, 2006
Earliest Anticipated Start Date: July, 2006

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 at the beginning of this document.

The letter of intent should be sent to:

Priti Mehrotra, Ph. D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 435-9369
FAX: (301) 402-2638
Email: pmehrotra@niaid.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. 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)

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

Priti Mehrotra, Ph. D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 435-9369
FAX: (301) 402-2638
Email: pmehrotra@niaid.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. Personal deliveries of applications are no longer permitted.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIAID. Incomplete and 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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

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 http://grants.nih.gov/grants/policy/policy.htm.

When clinical studies are a component of the proposed research, awards will be subject to the NIAID Clinical Terms of Award (information available at http://www.niaid.nih.gov/ncn/sop/ctoa.htm).

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 or competing continuation award if such costs: are necessary to conduct the project, and 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 or competing continuation 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.

Discretionary fund expenditures will be restricted until the process for solicitation, review, and ranking of proposed projects and/or research resources as described under Research Objectives and Scope above, is established by the Steering Committee as part of the Study Group Plan as described in Section VI.2.A.3 below. Once this process is established, discretionary funds will be available for distribution.

6. Other Submission Requirements

Applications for U19 grants must follow special application guidelines in the NIAID brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS; this brochure is available via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm. Multi-project grant applications must have two or more individual projects, at least one of which must specifically address type 1 diabetes, and may include scientific cores and an administrative core. Scientific cores must serve at least two individual projects within the multi-project grant, and may be modified by the Steering Committee in order to most effectively serve the needs and goals of the Study Group.

Specific application details for multi-project grant applications are available at http://www.niaid.nih.gov/ncn/grants/multi/3aa.htm. This brochure presents specific instructions for sections of the PHS 398 application form that should be completed differently than usual. For all other items in the application, follow the usual instruction in the most current PHS 398. Applicants are advised to review carefully the instructions and page limitations in the NIAID brochure and to discuss any questions with the Scientific/Research Contact listed in Section VII.1 below.

Applications for this RFA must include the following:

1. Program Overview (U19 applications only): A clear and concise plan that depicts the interrelationships among the research groups, their relevant experience and expertise, and the contribution of each to the fulfillment of the objectives of this RFA; an organizational chart of the U19 cooperative group showing the name, organization, and scientific discipline of the Principal Investigator and of all key scientific and technical personnel, as well as a discussion of lines of authority and plans for the coordination of research projects; and a plan to assure the maintenance of close cooperation and effective communication among members of the U19 group.

2. Research Plan, Project Goals and Milestones: A clear delineation of the research plan(s) and project goal(s) to be completed during the project period. The applicant must clearly state the interim objectives and milestones to be achieved during the project, identify their relevance to the prevention of autoimmune disease, and provide a detailed timeline for the attainment of each goal.

3. Scientific and Technical Expertise: Documentation of the scientific and technical expertise required to design, conduct and analyze the proposed studies. A broad range of scientific and technical expertise is required to carry out the objectives of this program, including extensive experience in: the study of basic animal and human immunology; mechanisms of autoimmunity and specific autoimmune diseases, including type 1 diabetes; genetics; molecular and cellular biology, particularly as applied to the identification and evaluation of biomarkers and assay development and validation; and human research involving clinical samples. Applications must include scientific expertise in these areas under the direction of a senior scientist serving as the Principal Investigator, with responsibility for the scientific, technical, and administrative coordination and management of the applicant group. The Principal Investigator is advised to devote at least 20% effort to the Study Group.

4. Commitment to the Collaborative Study Group: A written commitment from the Principal Investigator to serve on the Steering Committee, adhere to the policies and decisions reached by the Steering Committee, and accept the participation and assistance of NIH staff in accordance with the guidelines discussed in Cooperative Agreement Terms and Conditions of Award: NIH Staff Responsibilities. This includes participation in two face-to-face Steering Committee meetings in the first year and one annual meeting thereafter. At least one of the meetings in the first year will be held in the Bethesda, Maryland area.

5. Innovative Projects (not counted against page limits) : All applications must include two concise proposals, limited to 5 pages each, describing potential Innovative Projects as described under Research Objectives and Scope Discretionary Fund above. The purpose of these proposals is to demonstrate the applicant's ability to conceptualize and design novel studies. During its first competitive segment, the current Study Group has used discretionary funds to support Innovative Projects including novel collaborative, discovery-based, and pilot/feasibility studies, with the goal of surmounting barriers to progress and developing new fields for research into autoimmune disease prevention. The two proposed Innovative Projects should reflect the goals of the program and the nature of Innovative Projects as stated in Section I.1, Research Objectives and Scope Discretionary Fund, above, as well as the applicant's view of potential new areas for advances in the field of autoimmune disease prevention. The Innovative Project proposals should describe the specific aims, background and rationale, and proposed research plan. Proposed overall costs for each Innovative Project should be included in the five-page limit, but detailed categorical budgets should not be submitted, and costs for these Innovative Projects should not be included in the calculation of overall program costs. These proposed Innovative Projects will be evaluated by reviewers, and their scientific and technical merit will be reflected in determining the overall priority score.

6. Experience with Innovative Projects (not counted against page limits) : One-page summaries of projects previously undertaken by the Principal Investigator and/or project leaders that conform to the description of Innovative Projects under Research Objectives and Scope above. Such projects may include R03- or R21-type research grants or pilot/feasibility studies supported by this Study Group or other funding sources. The purpose of these summaries is to demonstrate the applicant's ability to select and conduct studies of this nature. Each summary should include: the title, dates, and amount and source of funding for each project; a description of the background and goals of the project, the results obtained, the reasons for success or failure of the project; and a list of publications or additional research support arising from each project. These summaries will be evaluated by reviewers as indicative of the applicant's ability to select and execute innovative projects, and this evaluation will be reflected in determining the overall priority score.

7. Overall Study Group Perspective (not counted against page limits): A clear and concise discussion, not more than two pages in length, outlining the applicant's vision and plan for the fulfillment of the broad goals of this RFA as described in Section I.1, Research Objectives and Scope above and specifically addressing the following questions:

What are the critical obstacles to progress in autoimmune disease prevention that should be addressed by the Study Group?
What are areas of opportunity and priority for collaboration and/or coordinated research by the Study Group?
What are the critical roles for Innovative Projects as described in Research Objectives and Scope above in fulfilling the goals of the Study Group?

This purpose of this discussion is to obtain each applicant's perspective on the Study Group and to provide a basis for the Study Group Plan to be developed by the Steering Committee. This description will not be factored into the priority score.

8. Budget Requests : Include travel funds for the Principal Investigator and Project Leaders to attend the annual Study Group meeting, and for Principal Investigators to attend Steering Committee meetings.

9. Authorization to Share Applications and Summary Statements with JDRFI (not counted in 25-page Research Plan limit) : A letter authorizing NIAID to share applications and summary statements for such applications with JDRFI. Letters of authorization are to be co-signed by the Principal Investigator and the official signing for the applicant organization.

Applicants are encouraged to contact NIAID program staff well in advance of the application submission date to discuss the proposed research program. This will also allow staff to assess responsiveness to this RFA and to provide appropriate guidance as needed with regard to this initiative. Discussion with program staff does not guarantee funding of an application.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

1. Criteria

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review
• Availability of funds
• Relevance to program priorities , including representation of a programmatically appropriate spectrum of autoimmune diseases

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific 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 advisory councils of the co-sponsoring NIH institutes.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Do the investigators present evidence of ability to work productively in a cooperative group and to select and execute pilot/feasibility projects?

Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

The general review criteria for U19 multi-project cooperative agreement applications are presented in the NIAID brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS at http://www.niaid.nih.gov/ncn/grants/multibron.htm. All applicants must also comply with the requirements detailed in Section IV.6, Other Submission Requirements.

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Innovative Project Proposals: The two proposals for Innovative Projects as specified in Section IV.6, Other Submission Requirements, will be evaluated using the NIH criteria of Significance, Approach and Innovation as a measure of their potential impact and relevance to the goals of this program.

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

2.B. Additional Review Considerations

Overall Study Group Perspective: The reasonableness and relevance of the applicant's vision and plan for the fulfillment of the broad goals of this RFA. The evaluation of the Overall Study Group Perspective will not be factored into determining the overall priority score.

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. Timely release of data to NIH-supported and/or public databases is expected in accordance with the NIH data sharing policy available at http://grants.nih.gov/grants/policy/data_sharing/.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not Applicable

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the Notice of Grant Award will be generated via email notification from the awarding component to the grantee business official (designated in item 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the Notice of Grant Award 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 NGA 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 notice of grant award. 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 (U01/U19), 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 objectives, approaches and details of the projects within the guidelines of this RFA; serving as a voting member of the Steering Committee; adhering to the policies and decisions adopted by the Steering Committee; and accepting the participation and assistance of NIH staff.

Monitoring Clinical Studies

If clinical research or clinical trials are a component of the research proposed, NIAID policy requires that 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.

All clinical research activities performed under this award must be in compliance with all U.S. Federal regulations, guidance and NIH policies applying to the conduct of research involving human subjects and regulatory application for new drug or biological licenses when applicable. These include, but are not limited to, U.S. Code of Federal Regulations (CFR) Title 21, Parts 11, 50, 54, 56, 312, 314, 601 and Title 45, Part 46; ICH guidance for Good Clinical Practice (GCP); and NIH grants policy (refer to http://grants1.nih.gov/grants/policy/nihgps_2003/index.htm).

Publication and Presentation of Study Findings

Early publication of findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of support by the Cooperative Study Group for Autoimmune Disease Prevention and the appropriate funding agencies (http://grants.nih.gov/grants/policy/nihgps_2001/part_iia_6.htm).

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 Scientific Coordinator will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

NIAID staff assistance will be provided by an NIAID Scientific Coordinator from the Autoimmunity Section, Clinical Immunology Branch, NIAID Division of Allergy, Immunology and Transplantation, or his/her designee. During the performance of this award, the NIAID Scientific Coordinator, with assistance from other scientific program staff who are designated based on the research topic and their relevant expertise, may provide appropriate assistance, advice, and guidance by: participating in the design of the activities of the Study Group; advising in the selection of sources or resources; advising in project management and technical performance; serving as liaison to other autoimmunity-related NIH programs including the Immune Tolerance Network, the Autoimmunity Centers of Excellence, and the Type 1 Diabetes TrialNet; recruiting external advisors to the Study Group from the international autoimmunity research community and soliciting their advice and attendance at Study Group meetings; and participating in the preparation of publications for collaborative projects, as appropriate. However, the role of the NIAID Scientific Coordinator will be to facilitate, and not to direct, the activities of the Study Group. It is anticipated that decisions in all activities will be reached by consensus and that NIH and JDRFI staff will be given the opportunity to offer and/or solicit ideas and opinions during this process. The manner of reaching consensus and the final decision-making authority will rest with the Study Group 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. An NIAID Program Official, who may also serve as the NIAID Scientific Coordinator, will be assigned to perform normal program stewardship responsibilities for the grants awarded under this RFA, including monitoring program progress and approving changes. The Government, via the NIAID Program Official, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIAID staff may use information obtained from the data for the preparation of internal reports on the activities of the Study Group. However, awardees will retain custody of and have primary rights to all data developed under these awards. All research projects conducted by the Study Group must be within the scope of the RFA and be approved by the NIAID Program Official and Grants Management Officer.

2.A.3. Collaborative Responsibilities

Steering Committee

A Steering Committee will serve as the governing body of the Study Group and will be responsible for development and implementation of the Study Group Plan (see below). At a minimum, the Steering Committee will be composed of the Principal Investigators of each of the awarded grants and the NIH Scientific Coordinator serving as a representative of the cosponsors. The Steering Committee or the NIH may identify and appoint other non-federal members, as appropriate. Each member of the Steering Committee shall have one vote. A Chairperson will be selected by the Steering Committee from among the non-federal Committee members. Subcommittees of the Steering Committee may be established as necessary. The Steering Committee will meet at least twice in the first year and at least annually thereafter. The NIAID Scientific Coordinator may assist the Chairperson in developing the meeting agendas and scheduling the meetings of the Steering Committee. Each Steering Committee member will be expected to participate in all meetings and other Steering Committee activities, such as conference calls and subcommittee meetings, as may be necessary to accomplish the work of the Study Group. Awardee members of the Steering Committee will be required to accept and implement policies and activities approved by the Steering Committee.

The Steering Committee will also be responsible for ensuring that the activities of all Study Group members are coordinated, productive, collaborative when appropriate, and directed toward the goals expressed in the Study Group Plan and the overall goal of developing preventive strategies for human autoimmune diseases. The Steering Committee will convene annual meetings of all Study Group-supported investigators to facilitate review of the progress of all projects. These meetings will also be attended by external expert advisors in the field of autoimmunity, nominated and invited by the Steering Committee for the purpose of providing additional advice to the Steering Committee and the cosponsors. The Steering Committee will make recommendations for continuation or redirection of ongoing projects, incorporation of additional expertise or resources needed for accomplishing project or program goals, and extensions and modifications to the Study Group Plan.

With the exception of the proposed Innovative Project, NIAID and the cosponsors intend to support the peer-reviewed studies proposed in the awarded grant applications. However, under special circumstances (e.g. duplicative or overlapping specific aims among awardees), the Steering Committee will establish guidelines and review procedures, and will evaluate and recommend to NIAID opportunities for collaboration, redirection, or modification of the peer-reviewed projects when applicable and necessary.

Discretionary Funds

It is anticipated that the Steering Committee will have access to additional discretionary funds to support:

• Pilot and feasibility studies designed to gather preliminary results in support of new grant applications focused on autoimmune disease prevention;
• Development and validation of novel reagents or animal models valuable for autoimmune disease prevention research;
• Hypothesis-driven studies of limited scope designed to complement or augment existing projects within the Study Group;
• Discovery-based studies designed to enable and/or stimulate hypothesis-driven research in autoimmune disease prevention;
• Modification or expansion of approved cores, or establishment of new cores, to serve the autoimmune disease prevention research projects of the Cooperative Study Group.

The Steering Committee will establish policies and procedures for the use of discretionary funding including:

• Soliciting, reviewing, and approving submission of proposed projects;
• Recommending budgetary support of meritorious projects;
• Monitoring progress and periodic review of projects; and
• Recommending continuation or discontinuation of projects.

Discretionary Fund Innovative Projects: Proposed Innovative Projects will be evaluated by reviewers, and their scientific and technical merit will be reflected in determining the overall priority score. Award of any cooperative agreement in no way implies that any of these proposed Innovative Projects will be implemented or funded. Innovative Projects to be funded by the Study Group will be selected by the Steering Committee based on the Study Group Plan, contingent on the availability of discretionary funds. The actual Innovative Projects undertaken by the Study Group thus may include both existing and new project concepts within the scope of the RFA.

In addition, the Chair of the Steering Committee will be responsible for the management of the discretionary funds and for reporting on discretionary fund expenditures.

Study Group Plan

The Steering Committee will be responsible for development of the Study Group Plan, which will articulate the goals, specify the approaches, and define milestones for the activities of the Study Group. The Study Group Plan will also detail procedures for solicitation, review and prioritization of proposals for Innovative Projects to be supported by the discretionary fund. The purpose of the Study Group Plan is to set an overall agenda for the Study Group's activities designed to produce maximum progress in the field of autoimmune disease prevention. It is anticipated that development of an optimal plan will involve consultation with external advisors from the international autoimmunity research community. The initial Study Group Plan will outline critical areas to be addressed through collaborative, coordinated, and/or pilot projects as described above. As part of the Steering Committee's annual review of all Study Group projects and activities, the Study Group Plan will also be reviewed and modified as necessary to address new opportunities and problems in the field.

Annual Report

The Steering Committee or a designated subcommittee will prepare an annual report, in paper and/or electronic format, containing at a minimum the following information: progress of ongoing and newly-initiated projects; progress toward milestones articulated in the Study Group Plan and additional directions and milestones adopted by the Study Group; manuscripts published, in press, and in preparation; presentations at regional, national, and international scientific meetings; ongoing and planned interactions with other NIH- and/or JDRFI-supported research programs; other activities of the group; and future plans.

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

The Steering Committee or a designated subcommittee will prepare an annual report, in paper and/or electronic format, containing at a minimum the following information: progress of ongoing and newly-initiated projects; progress toward milestones articulated in the Study Group Plan and additional directions and milestones adopted by the Study Group; manuscripts published, in press, and in preparation; presentations at regional, national, and international scientific meetings; ongoing and planned interactions with other NIH- and/or JDRFI-supported research programs; other activities of the group; and future plans.

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

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:

Thomas R. Esch, Ph. D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Room 3022, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601
Telephone: (301) 496-7104
FAX: (301) 480-1450
Email: tesch@niaid.nih.gov

Gilman Grave, M.D.
Endocrinology, Nutrition and Growth Branch
National Institute of Child Health and Human Development
6100 Executive Blvd, Room 4B11A
Bethesda, MD 20892
Telephone: (301) 496-5593
Email: graveg@exchange.nih.gov

Beena Akolkar, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 681
Bethesda, MD 20892
Telephone: (301) 594-8812
FAX: (301) 480-3503
Email: akolkarb@extra.niddk.nih.gov

Sally S. Tinkle, Ph.D.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
79 T. W. Alexander Drive 4401 Bldg.
Research Triangle Park, NC 27709
Telephone: (919) 541-5327
FAX (919) 541-5064
Email: stinkle@niehs.nih.gov

2. Peer Review Contacts:

Priti Mehrotra, Ph. D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616
Telephone: (301) 435-9369
FAX: (301) 402-2638
Email: pmehrotra@niaid.nih.gov

3. Financial or Grants Management Contacts:

Theresa Jarosik
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2261, MSC-7614
6700B Rockledge Drive
Bethesda , MD 20892-7614
Telephone: (301) 594-7460
FAX: (301) 480-3780
Email: tjarosik@mail.nih.gov

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.

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.

Public 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 public 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 RFA 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.

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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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 PA 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/ in the following citations: No. 93.855, Allergy, Immunology and Transplantation Research; No. 93.847, Diabetes, Endocrinology and Metabolism Research; No. 93.865, Child Health and Human Development Extramural Research; No. 93.113, Biological Response to Environmental Health Hazards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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/.

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NIH Funding Opportunities and Notices

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