Required Application Instructions

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

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

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

This FOA solicits 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 is a 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 (IOF) 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 continue the support for the CSGADP program. 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. The long-term goal of this program is to develop the knowledge base necessary to design selective interventions for the prevention of 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.

Autoimmune diseases are debilitating, chronic illnesses which collectively constitute an enormous disease burden and which currently lack 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. 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.

Although new treatments for many autoimmune diseases have come into clinical use over the past two decades, prevention of autoimmune diseases prior to clinical onset remains a worthy goal. 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 , 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. Similar conclusions were reached in The Future Directions of Lupus Research , a 2007 report from the Lupus Federal Working Group, which established Lay the foundation for lupus prevention as its first goal for future research. Subsequently, the 2011 Strategic Planning Report of the Diabetes Mellitus Interagency Coordinating Committee, Advances and Emerging Opportunities in Diabetes Research emphasized the value of research aimed at preventing type 1 diabetes as critical to reducing the burden of this disease.

A large body of evidence indicates that the autoimmune process may precede by years the development of clinical disease and that this preclinical autoimmunity may or may not develop into full-blown disease. 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 is often detectable years earlier. In addition, evidence of autoimmunity in healthy individuals (e.g., 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 healthy individuals. Similarly, in rheumatoid arthritis development of antibody responses to citrullinated autoantigens and elevated levels of cytokines and chemokines precede the onset of multiarticular pain and cartilage destruction. These findings collectively suggest the presence of control mechanisms in those individuals who remain healthy as well as an interval in which preventive interventions may be successful. 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 all needed.

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, corresponding 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. In humans, a multitude of studies have demonstrated that polymorphisms in specific immune-linked genes are often linked to multiple disparate autoimmune diseases. Clinical trials demonstrating efficacy of treatments based on common immune pathways, such as those involving TNF-alpha or IL-23, for a range of human autoimmune diseases suggest that such commonalities may also be exploitable for prevention of autoimmunity.

Key accomplishments from previous funding cycles of the CSGADP include detailing the relationship between serum markers of inflammation and autoimmunity and progression of preclinical rheumatoid arthritis, thus laying the groundwork for a phase II trial (NCT02603146) for prevention of rheumatoid arthritis in at-risk subjects; elucidation of autoantigen recognition in type 1 diabetes to the point that blocking activation of autoreactive T cells with small molecules is a realistic possibility; advances in our understanding of how genetic variants affect the function of regulatory T cells in both type 1 diabetes and multiple sclerosis; and development of 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 and resources in autoimmunity funded by NIH and private sources, including grants on the homing and function of regulatory T cells in autoimmune diseases and initial funding of the Network for Pancreatic Organ Donors (nPOD).

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, that is, by mechanisms which selectively target the autoimmune process and leave beneficial immune responses intact. 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 any interventions so developed may also be beneficial in established disease, the focus of this FOA is on prevention rather than therapy. The PDs/PIs of the applications funded under this FOA will form the Study Group and will, in collaboration with the NIH, 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.

Recent technological advances have greatly increased our ability to conduct informative studies using samples taken from humans at risk for, or diagnosed with, autoimmune diseases. Applicants are thus 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: 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. While animal models have historically been useful in the study of autoimmune diseases, it is also clear that animal models may not adequately mimic critical aspects of human autoimmune disease. Animal studies proposed under this FOA must therefore document the relevance of the model to the development of preventive strategies for human autoimmune diseases.

To promote rapid public access to CSGADP-supported data and results, all Program Directors/Principal Investigators (PDs/PIs) funded under this initiative will be expected to share their CSGADP-supported data publicly through ImmPort, ImmuneSpace, or other public portals designated by NIAID. The privacy of participants will be safeguarded and confidential and proprietary information will be protected. After award and prior to data collection, data set definitions and schedules for data sharing are expected to be negotiated with NIAID.

Research projects must contribute knowledge critical to achieving the goal of designing and administering practical interventions to prevent one or more autoimmune diseases. Broad areas of research subservient to this goal include but are not limited to:

• Pathogenic autoreactive T and B cell responses and their regulation by the immune system;
• The dysregulation of immune homeostatic mechanisms in preclinical autoimmunity and in autoimmune disease states;
• The role of genetic susceptibility and environmental influences in autoimmune disease;
• Biomarkers of disease risk, stage, activity, and immune responses;
• Pathways, mechanisms and means best suited to practical preventive interventions.

Specific research topics within these areas include, but are not limited to:

• Development and regulation of the immune response to self in healthy and autoimmune-prone infants, children and adults;
• Delineation of the phenotype and function of effector and regulatory T and B cell populations in target tissues and associated lymphoid organs;
• Definition of the role of the innate immune system in the maintenance and breakdown of immune homeostasis and tolerance;
• Studies to determine the mechanisms by which defined genetic risk alleles influence susceptibility to autoimmune disease;
• Studies of the metabolic state of immune cells in relation to autoimmune disease and its prevention;
• Determination of the function of antigen processing and the activity of antigen presenting cells in the development and maintenance of tolerance to self;
• Definition of biomarkers and risk factors to delineate populations that may benefit from interventions to prevent autoimmune disease;
• Practical approaches to target preventive 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 and application of clinically relevant animal models to facilitate the translation of preventive approaches from animals to humans;
• Identification and elucidation of cellular and immune pathways that may provide targets for preventive interventions.

Applications including the following types of studies will be considered non-responsive and will not be reviewed:

• Clinical trials
• 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.
• Studies on HIV and /or AIDS.

Applicants are encouraged to consult with the Scientific/Research Contact(s) before submitting their application.

Steering Committee

A Steering Committee will be established to direct the overall efforts of the Study Group, make recommendations regarding the use of the Infrastructure and Opportunities Fund, and evaluate the progress and direction of Study Group investigators. The Steering Committee will conduct at least one annual face-to-face meeting of all CSGADP investigators to review progress under the U01 awards and any projects funded by the Infrastructure and Opportunities Fund.

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 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 awardee institution will be selected by NIAID to administer the IOF. This institution must agree to take responsibility for managing the IOF with advice from the Steering Committee. Projects approved for IOF support will be funded as Consortium Agreements under the CSGADP award to the institution managing the project, and thus generate the same additional responsibilities as any project.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must obtain 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, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:

Maja Maric, Ph.D.
Telephone: 240-669-5025
Fax: 301-480-2408
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Other Attachments: The following attachment is required for this FOA, and must be included as a separate pdf attachment.

The filename IOF.pdf should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Applicants must provide a plan of how the IOF will operate to serve the CSGAPD. The responsibilities of the IOF will include disbursement and tracking of funds, ensuring regulatory compliance by the consortium agreements (e.g., IACUC approvals, human subjects reporting), and collection of materials for inclusion in the parent grant's annual progress reports. The IOF management plan must at a minimum cover the following points:

• Staffing levels and chain of responsibility to be devoted to IOF administration;
• Relevant experience and qualifications of the offices and individuals to be involved in IOF administration;
• Proposed measures and procedures for disbursement, reporting and monitoring of IOF expenditures. This should include time intervals for establishment and renewal of consortium agreements and for payment of invoices, plans for handling overdue or missing invoices, and plans for handling consortium agreements administration delays.
• Describe plans and procedures to ensure that all projects supported from the IOF will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in projects and appropriate ethical oversight.
• The plan should NOT include or propose specific projects to be funded from the IOF; these decisions will be made in conjunction with the steering committee after award.

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

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

The budget must include funds for travel to the Bethesda, MD area for two Steering Committee meetings within the first 12 months, and annually thereafter, for the PD/PI. For multi-PD/PI applications, the budget must include travel funds sufficient for all PDs/PIs to attend these Steering Committee meetings.

IOF Budget:

Applications must include a section with a separate budget justification for the $1,200,000 direct costs per year for the IOF. Within the Budget Justification applicants should justify the salary and effort of the IOF administrator.

Application budgets must include the following costs:

• Salary and calendar months for an IOF administrator to be included in the Other Personnel category.
• Costs for each pilot/feasibility project per year to be included in the Other Direct Costs category, assuming ten to twelve projects per year each with a maximum of $100,000 direct costs and a duration of one year.

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

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

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

Specific Aims: List the broad, long range objectives and goals of the proposed project and describe the work to be completed.

Research Strategy: Within the research strategy, applicants must include the following:

A clear description of how the proposed studies contribute knowledge critical to achieving the goal of designing and administering practical interventions to prevent autoimmune diseases.

If animal studies are included, provide a justification of the choice of the animal model and the relevance of any proposed animal studies to prevention of human autoimmune diseases.

Letter of Support: Infrastructure and Opportunities Fund Management - All applicants must include a letter from the PD(s)/PI(s) and the Institution's Signing Official agreeing to take fiscal responsibility for the management of the IOF, if chosen by NIAID to do so.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Applicants are strongly encouraged to address the specific datasets to be shared, the assignment of responsibility within the project for custody, curation and deposit of data in ImmPort or other public portals, the schedule for deposition of data into private database spaces and its transition to public availability.
• All Study Group investigators will be expected to share their Study Group-supported data publicly through ImmPort/ImmuneSpace, or other public portals designated by NIAID.

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

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

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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

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

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

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

Will the proposed studies contribute knowledge critical to achieving the goal of designing and administering practical interventions to prevent autoimmune diseases?

Are any proposed animal studies relevant to prevention of human autoimmune diseases and of high scientific merit?

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

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?

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

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

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 score, but will not give separate scores for these items.

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

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

Not Applicable

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

Infrastructure and Opportunities Fund Plan

Is provision of the proposed IOF management services to the program described in sufficient detail? Is sufficient justification provided for the management methods proposed for the IOF? Are the personnel charged with managing the IOF appropriate? Are adequate plans and procedures proposed by the applicant in the IOF plan to assure compliance with relevant federal regulations and NIH policies for the protection of human research participants, including the evaluation of risks and protections in project proposals, appropriate ethical oversight of funded projects, and plans for monitoring data and safety in clinical research projects?

Not Applicable

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).

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

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

Applications will be assigned 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 National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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

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

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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

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

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 Part 75, and other HHS, PHS, and NIH grant administration policies.

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

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

• Serving as a member of the Cooperative Study Group and participating in CSGADP activities;
• Acceptance and implementation of common guidelines approved by the CSGADP Steering Committee;
• Serving as a voting member of the Steering Committee (one PD/PI per award if multiple PD/PIs);
• Timely publication of major findings, with submission of manuscripts to the NIAID Project Scientist promptly upon acceptance for publication;
• Abiding by guidelines established by the Steering Committee for publication of results of collaborative projects;
• Acknowledgment of NIAID support, using the CSGADP grant number, in publications and oral presentations of work performed under this agreement. 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.
• Making data generated using CSGADP support publicly available while safeguarding the privacy of participants and protecting confidential and proprietary information as appropriate and consistent with achieving the goals of the program. Data set definitions and timelines for deposition in private database areas and release to the public are expected to be negotiated with NIAID as part of the data-sharing plan for each award and included as a Term and Condition of Award.
• Ensuring successful completion of the data- and other resource-sharing plans negotiated with NIAID as appropriate and consistent with achieving the goals of the program. Sharing plans represent a commitment by the applicant institution (and its subcontractors, if any) to support and abide by the plan.
• Establishing procedures to ensure that all CSGADP-supported investigators, including any scientists added via IOF support, conform to the data-sharing and other resource-sharing plans as appropriate. Final versions of NIAID-approved sharing plans will become a condition of the award.
• 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 Autoimmunity and Mucosal Immunology Branch, Division of Allergy, Immunology and Transplantation, NIAID, who will serve as the NIAID Project Scientist. The role of the NIAID Project Scientist will be to facilitate, and not to direct, the activities of the CSGADP. The NIAID Project Scientist will serve as a voting member of the Steering Committee.
• The NIAID Project Scientist will support CSGADP activities through technical assistance, advice and coordination of CSGADP activities. Support may be through selection of resources and identification of potential collaborations to further the goals of the program; acting as a liaison to other NIH programs; recruiting external advisors from the research community and soliciting their advice and attendance at Steering Committee meetings; and participating in the preparation of publications for collaborative projects, as appropriate.
• NIAID program staff will select the PD/PI and institution to manage and administer the IOF.
• 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 CSGADP. All CSGADP investigators, both recipients of U01 awards and recipients of IOF funding, will be required to accept and implement common guidelines and procedures approved by the Steering Committee.

• All U01 PD/PIs will serve as Steering Committee members. For multi-PD/PI awards, each PD/PI will serve of the Steering Committee, but each U01 will have only one vote.
• Each Steering Committee member will be expected to participate in all Steering Committee activities necessary to accomplish the work of the Study Group.
• NIH may appoint up to two external scientists or additional NIH staff to the Steering Committee as non-voting members. The Steering Committee may appoint additional non-voting members by majority vote
• A chairperson will be selected from among the non-Federal Steering Committee members.
• Subcommittees of the Steering Committee may be established as necessary.

The Steering Committee will:

• Serve as the governing body of the CSGADP;
• Identify scientific opportunities, emerging needs, and impediments to progress;
• Develop a 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. 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 Project Scientist. 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;
• Ensure that the activities of the CSGADP are coordinated, productive, collaborative when appropriate, and directed toward the goals expressed in the Study Group Plan;
• Provide guidance and recommendations to investigators and NIH staff regarding study implementation and conduct;
• Develop guidelines and policies for publication of the results of collaborative projects;
• Compile reports of CSGADP program activities and accomplishments, as requested by the NIH Project Scientist;
• Establish definitions and data collection standards for collaborative projects, as needed;
• Establish subcommittees as needed to provide recommendations on shared aspects of the CSGADP, including but not limited to the activities listed above;
• Oversee the use of the IOF (see below) by developing initiatives to be supported by the IOF, determining review criteria and processes for proposals for IOF use, and advising on funding plans using the IOF.

Infrastructure and Opportunities Fund (IOF):

• An Infrastructure and Opportunities fund is provided to support CSGADP activities consistent with the goals of this program and the CSGADP Study Group Plan, e.g. support of innovative projects, including pilot and feasibility projects; support of CSGADP collaborative projects initiated after U01 award; and development of reagents and resources, including cooperative resources.
• The Steering Committee will oversee the IOF. This responsibility includes determining the goals, priorities and evaluation criteria for use of the IOF; devising and implementing means to make the immunology research community aware of CSGADP IOF initiatives and to ensure appropriate participation by researchers outside the CSGADP; receiving and reviewing proposals for IOF-funded projects; and reviewing progress of IOF-funded projects at a CSGADP Steering Committee meeting.
• The Steering Committee's responsibility to conduct and oversee these activities is intended to encourage those cooperative and collaborative efforts, among both CSGADP members and the research community at large, that are best suited to achieve the goals of the program and to advance knowledge for the prevention of autoimmune disease.

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 Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Thomas R. Esch, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3565
Email: [email protected]

Maja Maric, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-5025
Email: [email protected]

Kim L. Cooper
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: (240) 669-2952
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.