Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Funding Opportunity Title	Cooperative Study Group for Autoimmune Disease Prevention (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	Reissue RFA-AI-05-026
Related Notices	February 25, 2016 - This RFA has been reissued as RFA-AI-16-003.
Funding Opportunity Announcement (FOA) Number	RFA-AI-11-034
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855; 93.856; 93.847
FOA Purpose	This FOA issued by the National Institute of Allergy and Infectious Diseases (NIAID), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, solicits applications from institutions or consortia of institutions to participate in a cooperative study group focused on prevention of human autoimmune disease. For the purpose of this FOA, prevention of autoimmune disease is defined as halting the development of an autoimmune disease prior to clinical onset by means other than global immunosuppression. The study group has as its foundation a set of cooperative agreements coordinated by a Steering Committee, and also draws upon an Infrastructure and Opportunities Fund to support a range of innovative, collaborative, and pilot/feasibility projects.

Posted Date	June 17, 2011
Open Date (Earliest Submission Date)	September 7, 2011
Letter of Intent Due Date	October 7, 2011
Application Due Date(s)	November 8, 2011, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	March, 2012
Advisory Council Review	May, 2012
Earliest Start Date(s)	July, 2012
Expiration Date	November 9, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite applications from single institutions or consortia of institutions to participate in the Cooperative Study Group for Autoimmune Disease Prevention (CSGADP, also referred to hereafter as the Study Group ).

The CSGADP [http://www3.niaid.nih.gov/about/organization/dait/CSGADP.htm] is a unique multi-center cooperative program established in 2001 as a closely interactive and collaborative network of investigators, with a focus on autoimmune disease prevention and a historical emphasis on type 1 diabetes. The Study Group has as its foundation a set of cooperative agreements coordinated by a Steering Committee, and also draws upon an Infrastructure and Opportunities Fund to support a range of innovative, collaborative, and pilot and feasibility projects 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, the mechanisms and consequences of manipulation of the immune response in autoimmunity, and the application of this information to the prevention of autoimmune diseases in humans. The purpose of this FOA is to announce continued support for the CSGADP program for a third funding cycle; both new and renewal applications will be accepted. 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 FOA, 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, which disproportionately afflict women, are debilitating, chronic illnesses that affect multiple organ systems and for which there are currently no preventive treatments or strategies. Type 1 diabetes afflicts over 600,000 persons in the United States with peak onset in childhood. Despite insulin treatment, long-term complications include kidney failure, blindness, amputations, and accelerated cardiovascular disease. Patients with type 1 diabetes are also at higher risk for 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 subclinical 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. Inflammatory bowel diseases (including Crohn’s disease and ulcerative colitis), characterized by abnormal immune responses that result in inflammation of the intestinal lining, afflict nearly a million persons in the United States and result in significant morbidity including over 1 million hospital visits per year.

The 1999 Institute of Medicine report, Vaccines for the 21st Century: A Tool for Decision Making, concluded that the development of antigen-specific tolerization approaches to treat or prevent type 1 diabetes, multiple sclerosis, and rheumatoid arthritis would bring exceptionally high economic and health benefits. The March 2005 report, Progress in Autoimmune Diseases Research, [http://www3.niaid.nih.gov/healthscience/healthtopics/autoimmune/PDF/ADCCFinal.htm], formulated by the Autoimmune Disease Coordinating Committee under the auspices of the NIH, also 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, development of biomarkers, and effective utilization of novel technologies and bioinformatics approaches. Subsequently, the 2007 Evaluation Report on the Special Statutory Funding Program for Type 1 Diabetes, [http://www2.niddk.nih.gov/NR/rdonlyres/70F78AD8-7E2D-44BD-8812-C03731E6A9C1/0/Type_1_Diabetes_Special_Funds_Complete_ReportSept2007.pdf] illustrated the significant progress that has been made in taking advantage of this additional targeted funding.

A large body of evidence suggests that autoimmunity or the autoimmune process may precede by years the development of clinical disease in type 1 diabetes, rheumatoid arthritis, 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) suggests that mechanisms to control autoimmunity may be operative in immune homeostasis in healthy individuals. Similarly, in rheumatoid arthritis development of citrullinated autoantigens, autoantibodies, and synovial cell activation and inflammation 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, identification of early markers or predictors of autoimmune processes, 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 the diagnosis of disease by months or years, 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 act as tolerogens 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 the onset of clinical disease without impairing protective immune responses appears feasible.

Objectives and Scope

This FOA will support a cooperative study group focused on research for the prevention of human autoimmune disease. For the purpose of this FOA, 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 Study Group will be comprised of a consortium of investigators who, in collaboration with the NIH, will develop and implement a Study Group Plan for autoimmune disease prevention. The Study Group Plan will articulate the goals, specify the approaches, and define milestones for the activities of the Study Group and will guide the Study Group Steering Committee in the allocation of an Infrastructure and Opportunities Fund [see Section VI.2, Cooperative Agreement Terms and Conditions of Award, "Areas of Joint Responsibility"].

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 FOA is on prevention rather than therapy. Key accomplishments from previous funding cycles of the CSGADP include identification of autoantigens for type 1 diabetes and potential biomarkers for the progression of preclinical rheumatoid arthritis, elucidation of novel mechanisms of peripheral tolerance in the setting of type 1 diabetes, and development of microarray and nanowell technologies for probing the development and progression of autoimmunity. In addition, the Study Group has used its Infrastructure and Opportunities Fund to foster the development of nine additional research projects in autoimmunity funded by NIH and private sources, including a genome-wide scan for genes conferring susceptibility to multiple sclerosis and grants on the homing and function of regulatory T cells in autoimmune diseases. Although the Study Group has historically maintained a strong interest and research program in type 1 diabetes, applications that include projects on other autoimmune diseases or projects related to more than one autoimmune disease are also encouraged.

Clinical studies are strongly encouraged; the use of human samples, including specimens obtained from clinical trials, is of obvious importance for the successful development of preventive strategies. Animal studies proposed under this FOA should document the relevance of the model to the development of preventive strategies for human autoimmune diseases.

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

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

• 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 and tolerance;
• Determination of the function of antigen processing and the activity of antigen presenting cells 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. 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. Studies of 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. Research topics include, but are not limited to:

• Practical approaches to target therapeutic 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 mechanisms;
• Analyses of the consequences of intervention approaches on both protective immunity and autoimmune responses;
• Development of practical means to identify patient 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.

Applicants are strongly encouraged to include studies involving human subjects and materials as an integral part of research projects. Examples of clinical studies that may be proposed include but not limited to: 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 FOA will not support the following:

Clinical trials (for definitions see http://funding.niaid.nih.gov/ncn/glossary/default2.htm#clintrial). Support for clinical trials resulting from research supported by the Study Group may be sought through arrangements with other programs, including but not limited to the Autoimmunity Centers of Excellence, the Immune Tolerance Network, or the Type 1 Diabetes TrialNet program.

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

Applications proposing above studies will be considered non-responsive and will not be reviewed.

Steering Committee

A Steering Committee will be established to direct the overall efforts of the Study Group, approve uses of the Infrastructure and Opportunities Fund, and evaluate the progress and direction of Study Group investigators. Steering Committee responsibilities are described further under Section VI.2, Cooperative Agreement Terms and Conditions of Award, "Areas of Joint Responsibility."

Infrastructure and Opportunities Fund

An Infrastructure and Opportunities Fund (IOF) will be made available after award to support Study Group activities and collaborative projects consistent with the goals of this program. The IOF may also be used to support new research opportunities not proposed at the time of award, including pilot projects proposed by Study Group members or other investigators, and development of reagents and resources in furtherance of the Study Group's mission.

After all Study Group awards have been issued, one or more awardee institutions will be selected by NIAID to administer the IOF. Applications from institutions with an interest in administering the IOF should include a letter of support from the business office as detailed in Section IV.2, Research Plan Component. All applicants shall submit budgets that reflect solely the needs of their individual applications and shall not include budgets for administration of the IOF. The IOF is described further under Section VI.2, Cooperative Agreement Terms and Conditions of Award, "Areas of Joint Responsibility."

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. NIAID and NIDDK intend to fund approximately 5-6 U01 awards, corresponding to a total of $2.6 million, plus an Infrastructure and Opportunities Fund, for fiscal year 2012. Future year amounts will depend on annual appropriations.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project. 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 for each project within a U01 grant has been $200,000 to $250,000 annual direct costs. Applicants may have valid reasons for deviating from this range, and are encouraged to discuss such deviations with the Scientific/Research Contact listed in Section VII below.
Award Project Period	In the interest of group cohesion, applicants should request and plan for a project period of five years.

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

Higher Education Institutions:

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For profit Organizations

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

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American tribal organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

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

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

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

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

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

The letter of intent should be sent to:

Priti Mehrotra, M.Sc., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Drive, Room 3138
Bethesda, MD 20892-7616
Telephone: 301-435-9369
FAX: 301-480-2408
Email: pm158b@nih.gov

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

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

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

Letter of Institutional Support for the IOF Administration Plan (optional)

Applications from institutions with an interest in administering the IOF should include a letter of support from the institutional business office detailing their plans for IOF administration. An institution chosen by NIAID to administer the IOF must agree to take responsibility for managing the IOF as directed by the Steering Committee. Projects approved by the Steering Committee for IOF support will be funded as subcontracts under the CSGADP grant to the institution managing the IOF, and thus generate the same additional responsibilities as any subcontract. The responsibilities of the IOF will include disbursement and tracking of funds, ensuring regulatory compliance by subcontractors (e.g. IACUC approvals, human subjects reporting), and collection of materials for inclusion in the parent grant's annual progress reports.

For planning purposes, applicants may assume that twelve IOF subcontracts will be issued each fiscal year, with an average cost of $100,000 and a typical duration of one year.

Prior to award, the site selected to administer the IOF will be asked to submit a budget for the costs of administration, with the final level of support to be negotiated with NIAID. Support for administrative costs may be allocated from the IOF.

Budget note: All PD/PIs will be required to attend an annual Study Group meeting, either in the Washington, DC area or at one of the member sites. The cost of this travel should be included in each individual project’s budget.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

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

Appendix

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

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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

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

This initiative is not subject to intergovernmental review.

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

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

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).

Expenditure of any Infrastructure and Opportunity Funds allocated to the Study Group under this FOA will be restricted to projects approved by the Steering Committee as meritorious and consistent with the goals of this program and the guidelines of the Study Group Plan.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIAID, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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

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

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Does the proposed research project contribute knowledge critical to advancing the understanding of immune homeostasis in autoimmune disease states as well as non-diseased states? Does the proposed research project contribute knowledge critical to the design and development of interventions to prevent human autoimmune diseases?

Investigator(s)

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

Innovation

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

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?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

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

Revisions

Not Applicable.

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

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.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIAID, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate Advisory Council l. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities. This may include representation of a programmatically appropriate spectrum of autoimmune diseases and/or approaches.

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

The PD(s)/PI(s) will have the primary responsibility for all aspects of the proposed studies. In addition:

• All investigators funded under this FOA, including recipients of IOF awards, are required to accept and implement policies and activities approved by the Steering Committee, including participation in an annual meeting of all investigators funded under this FOA.
• 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 agency and grant number. Early publication of major findings is encouraged. Publication of findings linked to clinical trials (for example, mechanistic studies that utilize samples from a clinical trial) must adhere to the policies enacted by the governing body of the clinical trial and the sponsor of the trial.
• 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 DHHS, PHS, and NIH policies.

NIH staff 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 a Program Official from the Clinical Immunology Branch, Division of Allergy, Immunology and Transplantation, NIAID, or his/her designee, who will serve as the NIAID Project Scientist. During the performance of this award, the NIAID Project Scientist, 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 Project Scientist will be to facilitate, and not to direct, the activities of the Study Group. The Project Scientist and other funding agency staff will participate in Steering Committee discussions as an integral part of the committee's decision-making process, with the goal of achieving consensus-based progress toward the goals elucidated in the Study Group Plan. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

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 Program Directors/Principal Investigators of each of the awarded grants, and the NIH Project Scientist serving as a representative of the funding ICs. The Steering Committee or the NIH may identify and appoint other members, as appropriate. A Chairperson will be selected by the Steering Committee from among the non-federal Committee members for an initial term of one year. The Steering Committee will meet at least twice in the first year and at least annually thereafter, and will reappoint the existing Chairperson or select a new Chairperson at each annual meeting. Subcommittees of the Steering Committee may be established as necessary. The NIAID Project Scientist 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.
• 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 meetings of all investigators (PIs of U01 awards and all investigators funded by the IOF) to facilitate review of the progress of all projects on an annual basis. The funding agencies may also invite external experts to attend these meetings for the purpose of providing additional advice to the Steering Committee and funding agencies. The Steering Committee will make recommendations to the NIAID Project Scientist 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.
• The Steering Committee will have access to an Infrastructure and Opportunities Fund (IOF) to support:
  • Study Group activities and collaborative projects consistent with the goals of this program and the Study Group Plan;
  • innovative pilot and feasibility projects; and
  • development of reagents and resources, including shared resources, required to accomplish the goals expressed in the Study Group Plan.
• The Steering Committee’s responsibility to conduct and oversee these activities is intended to encourage those cooperative and collaborative efforts, among Study Group members and the research community at large, that are best suited to achieve the goals of the program and to advance the field of autoimmune disease prevention. As part of this effort, the Steering Committee will devise and implement means to make the autoimmunity research community aware of the Study Group’s IOF project program and to ensure appropriate participation by researchers outside the Study Group. This will include establishment, with concurrence of the NIAID Project Scientist, of guidelines and procedures for solicitation and review of applications, funding levels, and monitoring progress of projects.

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 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, as facilitated by the NIAID Project Scientist. The initial Study Group Plan will outline critical areas to be addressed through collaborative, coordinated, and/or pilot projects as described above, and will be submitted to the NIAID Program Officer within six months of the initial award. 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.

Dispute Resolution:

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

When multiple years are involved, 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 the expenditure data portion of the Federal Financial Report are required for closeout of an award as described in the NIH Grants Policy Statement.

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

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

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Thomas R. Esch, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
6610 Rockledge Drive, Room 6606
Bethesda, MD 20892-6601
Telephone: 301-451-8851
Fax: 301-480-1450
Email: tesch@niaid.nih.gov

Beena Akolkar, Ph.D.
Immunopathogenesis and Genetics of Type 1 Diabetes Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Room 6105
Bethesda, MD 20892
Tel: 301-594-8812
Fax: 301-480-3503
Email: akolkarb@mail.nih.gov

Priti Mehrotra, M.Sc., Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
6700B Rockledge Drive, Room 3138
Bethesda, MD 20892-7616
Telephone: 301-435-9369
FAX: 301-480-2408
Email: pm158b@nih.gov

Dawn Mitchum, MPH, CRA
National Institute of Allergy and Infectious Disease (NIAID)
Division of Extramural Activities
6700B Rockledge Drive, Room 2113
Bethesda, MD 20892-7614
Telephone: 301-451-2667
FAX: 301-493-0597
Email: dmitchum@niaid.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.