Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Allergy and Infectious Diseases (NIAID)
Funding Opportunity Title	Autoimmunity Centers of Excellence, Basic Research Program (U19)
Activity Code	U19 Research Program Cooperative Agreements
Announcement Type	Reissue of RFA-AI-08-010
Related Notices	March 08, 2018 - This RFA has been reissued as RFA-AI-18-002. March 21, 2013 - See Notice NOT-AI-13-037. Pre-application Webinar and Teleconference.
Funding Opportunity Announcement (FOA) Number	RFA-AI-12-060
Companion Funding Opportunity	RFA-AI-12-059, Autoimmunity Centers of Excellence, Clinical Research Program (U19)
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.855, 93.856
Funding Opportunity Purpose	This FOA solicits applications to participate in the Autoimmunity Centers of Excellence (ACE) program, a cooperative network intended to improve the understanding and treatment of autoimmune diseases (www.autoimmunitycenters.org). The ACE program was founded on the premise that collaboration among basic and clinical scientists can accelerate both fundamental and applied research. For this reissued FOA, the formerly integrated Centers are divided into Basic and Clinical research programs. This FOA solicits applications for the Basic research program; a companion FOA solicits applications for the Clinical research program. The members of the Basic and Clinical ACE will work together to design and conduct studies of mechanisms of action of the immune-modulating agents being tested in the clinical trials. A Program Director/Principal Investigator (PD/PI) may NOT apply to both this ACE Basic program FOA and the companion Clinical program FOA.

Posted Date	January 15, 2013
Letter of Intent Due Date(s)	May 13, 2013
Application Due Date(s)	June 13, 2013
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October, 2013
Advisory Council Review	January, 2014
Earliest Start Date	May, 2014
Expiration Date	June 14, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 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. While some links are provided, 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.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of 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 ACE was founded in 1999, recompeted and expanded in 2004, and revised and recompeted in 2009. The ACE fosters collaborations among basic and clinical scientists with the goal of advancing our understanding of autoimmunity and accelerating the development of improved therapies for autoimmune diseases. Such collaborations have been productive but they are also difficult to create. This reissuance divides the ACE program into 2 components -- Basic and Clinical -- to better align grant awards with responsibilities. The Basic research program will provide a solid scientific foundation and will conduct advanced investigations into human immunology. The Clinical research program will develop and conduct Clinical Projects: clinical trials with integrated mechanistic studies. The members of the Basic and Clinical programs will work closely together to fully develop and conduct Clinical Projects.

Clinical trials with integrated mechanistic studies that are designed to "utilize materials and data from clinical trials to elucidate underlying mechanisms of drug activity and immune response" were advocated in the 2005 Autoimmune Diseases Research Plan by the Trans-NIH Autoimmune Diseases Coordinating Committee. The Plan also acknowledged that clinical trials are lengthy, risky, and expensive, conceding "many agents that show promising results in preclinical studies do not advance to clinical trials" and noting that new treatments are sometimes discovered "when practitioners identify new uses for medications originally approved for other conditions". The importance of informative clinical trials in developing new therapies and evaluating existing therapies was also emphasized by expert panels convened by the Institute of Medicine, most recently by a panel convened in November 2011 ("Envisioning a Transformed Clinical Trials Enterprise in the United States: Establishing an Agenda for 2020" pre- publication Clinical Trials Workshop Summary). Well-designed clinical studies of immune modulating agents can be fundamentally informative whether or not an investigational agent ultimately advances to licensure and clinical practice.

The purpose of this FOA is to solicit applications for the reissuance of the Autoimmunity Centers of Excellence (ACE) program. The goal of the ACE is to conduct insightful analyses of human immunology within and among collaborative Centers and especially in the context of Clinical Projects, i.e., clinical trials with integrated mechanistic studies. For this reissuancel, the formerly integrated Centers are divided into Basic and Clinical programs. This FOA solicits applications for the Basic research program; a companion FOA (RFA-AI-12-059) solicits applications for the Clinical research program. The members of the Basic and Clinical ACE will work together after award to design, fully develop, and conduct studies of mechanisms of action of the immune-modulating agents being tested in clinical trials with integrated mechanistic studies.

A Basic ACE possesses the following components:

Center Research Agenda (Program Overview): Applicants must set forth their perspectives on the fields of autoimmune disease research and therapy including the theme and goals of the Center, the most important questions to be answered, and a description of how the work of the Center will answer these questions. The applicants should also describe how the projects proposed within this application relate to the Center’s Research Agenda, how they would receive benefit from the ACE collaboration, and how they would benefit the ACE.

Principal Project: Applicants must propose a single Principal Project designed to advance our understanding of autoimmune disease in humans. This project should incorporate the theme of the Center’s Research Agenda, exploit the applicant’s expertise, and test hypotheses through Specific Aims that explore an area that is important to our mechanistic understanding of autoimmune diseases. The Principal Project must include a 5 year research plan and annual benchmarks for evaluating progress.

Pilot Project: Applicants must propose a single Pilot Project that should be innovative and exploratory, pursuing intriguing observations that may lead to discoveries or even breakthroughs. Preliminary data requirements are lower than for the Principal Project. The Pilot Project must include a 2 year research plan and benchmarks for evaluating progress at 18 months. The Pilot Project may be extended, expanded, or replaced after 2 years based on the Steering Committee’s evaluation of progress.

Collaborative Project: Applicants to the Basic program must propose a single Collaborative Project to test at least one specific hypothesis on the nature of human autoimmunity, exploit particular strengths of the applicant, and be designed to engage other members of the ACE after award. The Aims should exceed the reach of a single investigator and produce a greater-than-additive return. It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the ACE will not be known before award; therefore, applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans. The Collaborative Project must include a 5 year research plan and annual benchmarks for evaluating progress. The ACE will fully develop the Collaborative Projects after award and they will become part of the ACE Research Agenda (see below).

Note: Applicants to the ACE Basic Research Program CANNOT propose Clinical Projects. For more information on Clinical Projects, refer to the companion FOA RFA-AI-12-059.

Administrative Core (required): Applicants must request funds and justify their use to coordinate the Center activities.

Scientific Core (optional): Applicants may request support for one scientific core that provides materials and/or services to at least 2 Projects. This core must not replicate the functions of the statistical and clinical coordinating center, SACCC (see below). After award, this core may also provide materials and/or services to other members of the ACE.

ACE Funds Management Core (optional): The ACE program will be awarded a Clinical Project Fund, for support of the Clinical Projects, and an Opportunity Fund, for support of the Collaborative Projects and additional studies required for achieving the aims of the ACE Research Agenda. Applicants may propose an ACE Funds Management Core to administer these funds on behalf of the entire group.

The ACE will coordinate its activities through a Steering Committee, which will formulate an ACE Research Agenda and manage resources to complete the Agenda. These elements are described below.

ACE Program: The ACE Clinical and Basic programs will interact through the following elements:

Steering Committee: The work of the ACE will be coordinated by a Steering Committee formed with the PDs/PIs of the Basic and Clinical programs. The Steering Committee will, within 6 months of award, collaboratively formulate the ACE Research Agenda and post it on the public website (www.autoimmunitycenters.org). The Steering Committee will execute the Agenda by fully developing and conducting Clinical Projects and Collaborative Projects and managing resources, including reviewing applications to the Clinical Projects Fund and Opportunity Fund. The Steering Committee will monitor work and post on the public website an annual report on the progress toward the goals of the Agenda.

ACE Research Agenda: The Steering Committee will formulate an ACE Research Agenda that includes overarching themes, goals, and approaches for the period of award. The Agenda should incorporate the best ideas from the individual Centers' Research Agendas as well as the Collaborative Projects and the Clinical Projects.

Plenary Meeting: The ACE will convene an annual plenary meeting to develop collaborations among the investigators. The aims and status and highlights of all projects from all Centers will be presented in brief talks. All key personnel, including project leaders, are expected to attend and participate. The initial plenary meeting will be held in Bethesda, Maryland soon after award.

These elements will help enable, coordinate, and direct collaborations among the Centers and Projects.

The objectives of the ACE are to accelerate the discovery and translation from lab to clinic of therapies for autoimmune diseases. The ACE approaches these objectives by conducting cooperative basic, clinical, and mechanistic studies, fostering intellectual and material collaborations among basic and clinical scientists, and facilitating the study of clinical samples by basic research scientists. These approaches are expected to identify common and distinct mechanisms in the pathogenesis of autoimmune diseases.

Research Scope: All projects must investigate autoimmune disease in humans. Projects designed to test explicit hypotheses are preferred over projects designed to collect data.

Principal, Pilot, and Collaborative Projects: These Projects may use samples from previously completed clinical trials but they may not support a clinical trial. For these Projects, specific areas of interest include, but are not limited to:

• Pathogenesis of human autoimmune disease;
• Mechanisms of action of existing therapies;
• Biomarkers for autoimmune disease status, including diagnosis, disease progression, prediction of remission or relapse, therapeutic response, and stratification;
• Sex-based differences in autoimmune disease;
• Mechanisms responsible for the initiation, maintenance, or loss of tolerance;
• Cellular analysis for diagnosis or therapy, including adult stem cells, regulatory B and T cells, and antigen-presenting cells;
• Single-cell or clonal analysis of genetic variation (including epigenetic) contributing to autoimmunity;
• Influence of histocompatibility genes (e.g., HLA) on autoimmunity; and
• Novel approaches to therapy through advances in fundamental immunity and biology, such as regulating gene transcription (methylation, acetylation), RNA metabolism (splicing, stability, miRNA, RNAi), Natural Killer (NK) inhibitor receptors (KIR), and proteins mediating signal transduction (immune synapse, intracellular pathways).

The Principal, Pilot, and Collaborative Projects will NOT support:

• Large scale epidemiology studies;
• Research using animal models of human disease;
• Clinical trials.

Note: Application on these topics are nonresponsive and will not be reviewed.

Statistical, Data Management, Pharmacy, and Operations Support

NIAID will provide statistical, data collection and management, pharmacy, and clinical trial operations support through a separately funded Statistical and Clinical Coordinating Center for Autoimmune Diseases Clinical Trials (SACCC-ADCT) contract. Each participating institution will be responsible for providing primary study data to the SACCC-ADCT. Timeliness and accuracy of submitted data will be monitored by the SACCC-ADCT and evaluated by the Steering Committee. SACCC-ADCT responsibilities are further described under Section VI Cooperative Agreement Terms and Conditions of Award Collaborative Responsibilities.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Renewal The OER Glossary and the PHS 398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIAID anticipates awarding up to $5 million in total costs in FY 2014 to fund up to 5 new or renewal grants within the ACE Basic program. Additional funds will be awarded to a single ACE institution to support the Clinical Project Fund and an Opportunity Fund. Future year amounts will depend on annual appropriations.
Award Budget	Applicants to the ACE Basic program can request up to $1 million in total costs to support the program, including the Principal, Pilot, and Collaborative Projects, Administrative Core, and the [optional] scientific core. See special budget instructions for each Project & Core. Support for the optional ACE Funds Management Core is limited to $250,000 per year in direct costs.
Award Project Period	Scope of the proposed project should determine the project period. The maximum period is 5 years.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

Applicant organizations must complete the following registrations as described in the PHS 398 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.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) 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 6 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(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 PHS 398 Application Guide.

Each individual Project and Core must be led by a single Project or Core Leader. Multiple PDs/PIs for projects and cores are not allowed.

The Administrative Core must be headed by the PD/PI or one of the PD/PIs on a multi- PD/PI application.

An individual may serve as PD/PI on an application to either this ACE Basic program FOA or the companion Clinical program FOA but not both. PD(s)/PI(s) should commit at least 2.4 person months effort (total for multiple PDs/PIs). A PD/PI may lead no more than one of the proposed Projects. The PD/PI (or one of the PDs/PIs if multiple PD/PIs) should also lead the Administrative Core.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. The same institution may also apply to the companion FOA. A single PD/PI, and PDs/PIs on a multiple-PD/PI application, may NOT also serve as PDs/PIs on an application to the companion FOA.

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

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

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS 398 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(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:

Paul Amstad, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3121, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-402-7098
FAX: 301-480-2408
Email: [email protected]

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

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

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Paul Amstad, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3121, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817-7616 (for express/courier service; non-USPS service)
Telephone: 301-402-7098
FAX: 301-480-2408
Email: [email protected]

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• Center Research Agenda (Program Overview): 12 pages
• Principal Project: 12 pages
• Pilot Project: 6 pages
• Collaborative Project: 12 pages
• Administrative Core (required): 6 pages
• Scientific Core (optional): 6 pages
• ACE Funds Management Core (optional): 6 pages

The following sections supplement the instructions found in Form PHS 398 for preparing a multi-project grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-project applications consisting of research projects interrelated by a common theme.

The multi-component grant application should consist of the following components:

• Center Research Agenda (Program Overview)
• Principal Project: required and limited to one
• Pilot Project: required and limited to one
• Collaborative Project: required and limited to one
• Administrative Core: required
• Scientific Core: optional
• ACE Funds Management Core: optional

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Form Page 1 - Face Page (Center Research Agenda)

Complete items 1 14 as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

Form Page 2. Summary, Relevance, Project/Performance Site, Senior/Key Personnel, Other Significant Contributor, and Human Embryonic Stem Cells (Center Research Agenda)

Description: Using PHS 398 Form Page 2; provide a succinct but accurate description (abstract) of the OVERALL multi-component application addressing the major, common theme of the program. Do not exceed the space provided.

Project/Performance Site: List the performance sites where the research will be conducted.

Senior/ Key Personnel: Under "Key Personnel", list the PD/PI(s) of the application, followed by the Leaders of the Projects and Cores, and co-investigators.

Form Page 3 - Table of Contents (Center Research Agenda)

Do NOT use Form Page 3 of the PHS 398; a more comprehensive table of contents is needed for a multi-project application.

Bearing in mind that the application will be scientifically reviewed component by component and core by core, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall application as well as to each component research project and core. Further, each component should be identified by number (e.g. Component 1), title, and responsible Leader, and each Core should be identified by letter (e.g. Core A), title, and responsible Core Leader. Provide the page numbers for the budgets of each component and each core. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

ITEMS (in order of appearance in application)

Application Package Cover Letter (optional). The cover letter is not provided to reviewers.

Face Page (use PHS 398 Form Page 1). This is the first numbered page of the application; number all succeeding pages consecutively.

Program Description (use PHS 398 Form Page 2) Project/Performance Sites, Senior Key Personnel and Key Personnel, Other Significant Contributors, Human Embryonic Stem Cell statement if applicable.

Table of Contents (do NOT use PHS 398 Form Page 3; Instead, use a Continuation Format Page and follow instructions above)

Composite Budget for Entire Proposed Project Period (do NOT use PHS 398 Form Page 4). Instead, use a Continuation page. See example and follow instructions below.

Center Research Agenda (Program Overview)

Project 1: Principal Project

Project 2: Pilot Project

Project 3: Collaborative Project

Core A: Administrative Core

Core B: Scientific Core (optional)

Core C: Funds Management Core (optional)

Appendix

Biographical Sketches (Biographical Sketch Format Page). Provide biographical sketches of all senior/key professional personnel here. Place PD/PI biographical sketch(es) first, followed by those of other senior/key personnel in alphabetical order.

Checklist (Checklist Form Page, last page of application)

Form Page 4 and 5 Composite Budget (Center Research Agenda)

Do NOT use PHS 398 Form Page 4. Instead, use the suggested format presented below to prepare a Composite Budget for All Proposed Years of Support. (Justification for budget items should NOT be presented here but instead in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Budget; Direct Costs for All Proposed Years of Support. Add additional Cores as appropriate to this FOA.

Cost Categories	Yr 1	Yr 2	Yr 3	Yr 4	Yr 5	All Years
Project 1: Principal Project	250,000	250,000	250,000	250,000	250,000	1,250,000
Project 2: Pilot Project	100,000	100,000	100,000	100,000	100,000	500,000
Project 3: Collaborative Project	250,000	250,000	250,000	250,000	250,000	1,250,000
Core A: Administrative Core	50,000	50,000	50,000	50,000	50,000	250,000
Core B. Scientific Core (optional)	50,000	50,000	50,000	50,000	50,000	250,000
Totals	700,000	700,000	700,000	700,000	700,000	3,500,000

Notes: The Center Research Agenda does not have its own budget. If proposed, provide a budget for Core C, the (optional) Funds Management Core, only within its description (see C.4, below), not here. Please note that the total costs may not exceed $1 M.

Biographical Sketch Format Page (Center Research Agenda)

Do not include here. Biographical sketches of all professional personnel for all components should be placed together at the end of the application with the PD(s)/PI(s) first, followed by those of other key personnel in alphabetical order.

Resources Format Page (Center Research Agenda)

Do not include here. Essential information is to be presented in the individual research project and core sections of the application as applicable.

Research Plan (Center Research Agenda)

Specific Aims: List in priority order the broad, long-range objectives and goals of the Center. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Research Strategy: This narrative section summarizes the overall research strategy for the multi-project application and explains how the proposed Program satisfies the purpose and all objectives of this FOA as outlined in Section I. Applicants should provide here their perspectives on autoimmune disease research and therapy. Include, for example, the directions the field should be taking, the most important questions to be answered, and how this Program advances the field. Also describe how the projects proposed within this application would provide benefit to, and benefit from, the ACE. The Center Research Agenda will become part of the ACE Research Agenda.

Applicants should describe the central theme of the proposed Program and explain how the proposed Principal, Pilot, and Collaborative Projects fit under the overarching Program theme. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section because it provides an opportunity for the group of investigators to give conceptual wholeness to the overall program by stating the general problems and by presenting a comprehensive strategy for attacking them. As the strategy develops, the projects and core(s) should be placed in the overall scheme. Also describe how the individual research projects and cores coordinate and synergize towards fulfilling the central theme and objectives of the Program.

Summarize the special features in the environment and/or resources that make this application strong or unique. Describe the experience of the investigators in developing and conducting collaborative research and highlight any participation in clinical trials with mechanistic studies. List accomplishments and describe the synergy and collaborations that occurred.

If the application is a renewal, this section should also highlight past performance and the major accomplishments from the prior funding period as described in the PHS 398 Instructions. In addition to discussing results from individual projects, describe the synergy and collaborations that occurred within the Program. For individual research projects and cores that will be continued as part of a renewal application, additional details should be provided in the progress report section of the Research Strategy within each research project and core.

Advisory Committee (optional): If you propose to appoint an advisory committee, describe the expertise and responsibilities of the potential committee members. For a new application, do NOT contact, recruit, or name potential members. For a renewal application, provide the names of current and former members.

Leadership Succession Plan: Provide a brief plan in the case the PD/PI moves to a different institution or is for any reason unable to continue as leader of the program.

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 PHS398 Application Guide.

Checklist (Center Research Agenda)

One Checklist, placed at the end of the application, is to be submitted for the entire application.

Cover Page (Principle, Pilot, and Collaborative Projects)

Repeat this section for each of the three required research projects: (1) the Principal Project, (2) the Pilot Project, and (3) the Collaborative Project.

Project Number and Title: (e.g., 1. Preclinical Evaluation of HIV Microbicides)

Name of Project Leader: (e.g., Jones, Roberta A.)

Human Subjects: (Yes or No)

If Yes:

Exemption number, -or-

IRB Approval Date (e.g., 12/13/2012,or "Pending"), and Federalwide Assurance (FWA) number

Vertebrate Animals: (Yes or No)

If Yes:

IACUC Approval Date (e.g., 11/17/2012, or Pending) and Animal welfare assurance number:

Proposed Period of Support:

• From: (mmddyy - e.g., 07/01/2013)
• To: (mmddyy - e.g., 06/30/2018)

Costs Requested for Initial Budget Period: (e.g. 07/01/2013-06/30/2014)

• Direct Costs: (e.g., $ 150,000)
• Total Costs: (e.g., $162,000)

Costs Requested for the Entire Budget Period: (e.g., 07/01/2013-06/30/2018)

• Direct Costs: (e.g., $700,000)
• Applicant Organization (full address)

Form Page 2. Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells (Principle, Pilot, and Collaborative Projects)

Description: Provide a Description (abstract) of the research proposed in the individual research project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the individual research project will contribute towards attainment of the multi-project Program objectives.

Project/Performance Sites: List the performance sites where the research will be conducted.

Key Personnel: Under "Key Personnel", list the Project Leader, followed by other key project personnel, and then other significant contributors.

Form Page 3. Table of Contents (Principle, Pilot, and Collaborative Projects)

Prepare a Table of Contents for the research project using Form Page 3 of the PHS 398.

Form Page 4 and 5. Detailed Budget for Initial and Entire Budget Period (Principle, Pilot, and Collaborative Projects)

Prepare a detailed budget and justification for the research project using Form Pages 4 and 5 of the PHS 398.

Principal Project: A scope and budget similar to a modular R01 grant is suggested ($250,000 annual direct costs for 5 years).

Pilot Project: A scope and budget similar to an R21 grant is suggested ($100,000 annual direct costs but for 5 years.) Extending the Pilot Project beyond 2 years will be at the discretion of the Steering Committee.

Collaborative Project: A budget for each proposed collaborator not exceeding a modular R01 grant is suggested ($250,000 annual direct costs for 5 years). The scope depends on the number of collaborators involved. See additional instructions in the Research Plan section below.

Research Plan (Principal, Pilot and Collaborative Projects)

Specific Aims: List the broad long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual research project's relationship to the Program’s goals and how it relates to other projects or cores. For the Collaborative Project, applicants should propose Specific Aims that test at least one hypothesis on the nature of human autoimmunity.

Research Strategy: Use this section to describe how the proposed research will contribute to meeting the Program’s goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and References Cited section and need not be detailed in the Research Strategy. Preliminary Studies for projects should be included as part of the approach section, and must be contained within the page limits of the Research Strategy section.

Progress Report for Renewal Projects: For renewal projects within renewal applications, provide a Progress Report. Include the beginning and ending dates for the period since the last competitive review and the previous specific aims and describe the progress made toward their achievement. Summarize the major accomplishments from the prior funding period and the importance of the findings. Explain any significant changes to the specific aims and any new directions including changes resulting from significant budget reductions. A list of publications, manuscripts accepted for publication, patents, and other printed materials should be included in the bibliography (do not repeat that information here).

Collaborative Project

The Collaborative Project must be closely related to the overarching theme of the applicant's proposed Center. Applicants should provide a research plan that exploits not only the applicant's strengths but will also benefit from the expertise of members of the network. It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the ACE will not be known before award; therefore, applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans. For example, applicants may start from their own specific expertise and disease focus and seek to generalize observations and mechanisms to other autoimmune diseases. This could be accomplished with collaborators who have complementary strengths and skills. The Collaborative Project must be coherent but it may lack some details if they can be reasonably developed with additional ACE collaborators after award.

Applicants should provide evidence of their success in previous collaborations (publications, patents, etc.) in the form of an annotated bibliography.

The Collaborative Projects will be fully developed after award and conducted with other members of the ACE. They will be integrated into an ACE Research Agenda. The Collaborative Project should include:

• A 5 year research plan with scope and Specific Aims consistent with the goals of the ACE;
• A description of the interaction, intellectual as well as material, among possible collaborators;
• A description of how this Collaborative Project will benefit, and receive benefit from, the collaborative ACE;
• Benchmarks for annual progress;
• A budget of up to $250,000 in direct costs per year.

A direct award will be made but the final budget for the collaborative project will be decided after the ACE Research Agenda has been developed. Additional funding will be determined post-award and will be guided by the final form of the ACE Research Agenda.

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 PHS 398 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.

Resources Format Pages (Principle, Pilot, and Collaborative Projects)

Provide information on resources available for the project. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site.

Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Biographical Sketch Format Page (Principle, Pilot, and Collaborative Projects)

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide, with the following modification:

• For each project, 3 publications plus other approved material are allowed.

Cover Page (Administrative, Scientific, and ACE Funds Management Cores)

The Face Page of the 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the 398 continuation page to create a "Cover Page" containing selected data about each individual core. This Cover Page will demarcate each core and should contain the following information items (which are a subset of the information provided on a Face Page - see PHS 398):

Core Letter and Core Title: (e.g., A. Monoclonal Antibody Production Core)

Name of Core Leader: (e.g., Smith, Robert A.)

Human Subjects (Yes or No)

If Yes,

Exemption Number, -or-

IRB Approval Date (e.g., 5/14/12, or Pending), and Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)

If Yes,

IACUC Approval Date (e.g., 4/15/12, or Pending), and Animal welfare assurance number

Proposed Period of Support

• From: (mmddyy, e.g., 07/01/2013)
• To: (mmddyy, e.g., 06/30/2018)

Costs Requested for Initial Budget Period

Direct Costs (e.g. $50,000)

Total Costs (e.g. $70,000)

Costs Requested for the Entire Budget Period

• Direct Costs (e.g. $212,323)
• Total Costs (e.g. $297,252)

Applicant Organization (ABC University; 111 Main Street; Anywhere, Else 99999)

Form Page 2. Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells (Administrative, Scientific, and ACE Funds Management Cores)

Description: Provide a Description (abstract) of the core activities and services according to the instructions on Form Page 2 of the PHS 398. In addition, the abstract should contain a brief description of how the core services will contribute towards attainment of the objectives.

Project/Performance Sites: List the performance sites where the core activities and services will be conducted.

Key Personnel: Under "Key Personnel", list the Core Leader, followed by other key core personnel, and then other significant contributors.

NOTE: The Administrative Core must be headed by the PD/PI or one of the PD/PIs on a multi- PD/PI application.

Form Page 3. Table of Contents (Administrative, Scientific, and ACE Funds Management Cores)

Prepare a Table of Contents for the core using page 3 of Form PHS 398.

Form Page 4 and 5. Budget Pages (Administrative, Scientific, and ACE Funds Management Cores)

Prepare a detailed budget and justification for the core using Form Pages 4 and 5 of the PHS 398.

Place all the individual Core budgets within this section together with justifications.

Note: Each core must be headed by a Core Leader with at least 0.6 person months effort committed to the Core. Include Biographical Sketches among those at the end of the overall application.

Administrative Core. A budget with justifications must be provided. Funds should also be budgeted for attending the twice-yearly Steering Committee face-to-face meetings, one of which will overlap with the annual ACE plenary meeting held in the Bethesda MD area.

Scientific Core (optional): Basic ACE applicants may request support for a scientific core. A budget of up to $50,000 direct costs is suggested. Additional support may be available after award if the Core provides services to other ACE awardees.

ACE Funds Management Core (optional): Applicants may also request support for a Funds Management Core to administer the Clinical Project Fund and Opportunity Fund. The budget for this Core must be entirely separate from the other elements. The plans and budget should be scaled to administer 60 contracts with 30 different sites amounting to $5M annually. In the proposed budget for the Funds Management, please include the Facilities and Administrative (F&A) costs that will be incurred by the institution to administer each consortium agreement in accordance with the Institution’s negotiated F&A Rate Agreement. The proposed budget for the FM Core must be provided and is capped at $250,000 (direct costs) per year. The ACE Funds Management Core should be headed by a Leader committing at least 0.6 person month effort. The budget request must include travel funds for the Core leader to attend the face-to-face Steering Committee meetings.

Research Plan (Administrative, Scientific, and ACE Funds Management Cores)

Specific Aims: For each of the required and optional cores, list in priority order the broad, long-range objectives and goals of the proposed core. In addition, state the core’s relationship to the Program’s goals and how it relates to two or more individual research projects or other cores in the application.

Research Strategy

Administrative Core: Organize the research strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Provide a Staffing and Administrative Plan that includes a discussion of the structure and roles of administrative and scientific staff, including, the committed level of effort, the training and experience of proposed staff and the functions to be performed; how resources will be prioritized, allocated and managed. Provide overall milestones, timelines and performance objectives in a section of entitled Milestones and Timelines , which must include also those of all Core activities. Provide a management plan for fiscal accountability and communication within the Center.

Scientific Core: Organize the research strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Use this section to describe how the proposed core activities will contribute to meeting the Program's goals and objectives and explain the rationale for selection of the general methods and approaches proposed to accomplish the specific aims. In addition, this section should indicate the relevance of the core to the primary theme of the application and how the core will contribute to the ACE.

ACE Funds Management Core: Applicants proposing a Funds Management Core must submit a plan to fulfill the responsibilities associated with the disbursement, administration and reporting on the use of the funds, including but not limited to the following:

• Administrative structure that should include a chief administrator;
• Procedures to inform the Steering Committee about the financial planning and monitoring of trials, studies, and projects supported by the CPF and OF;
• Processes for negotiating and awarding annual contracts and paying monthly invoices;
• Plans for interacting with investigators who are requesting or receiving funds, and a
• Format for a monthly overview and an annual detailed report on the status of Funds that must be submitted to NIAID.

Organize the research strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5. Provide a Staffing and Administrative Plan that includes a discussion of the structure and roles of administrative and scientific staff, including, the committed level of effort, the training and experience of proposed staff and the functions to be performed; how resources will be prioritized, allocated and managed. Provide overall milestones, timelines and performance objectives in a section of entitled Milestones and Timelines , which must include also those of all Core activities. Provide a management plan for fiscal accountability and communication within the Center.

• Describe the experience of the proposed Funds core managers and environment, including:
• Experience in administering contracts;
• Qualifications of the core leader and staff;
• Documented institutional commitment to this core.

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 PHS 398 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.

Resources Format Page (Administrative, Scientific, and ACE Funds Management Cores)

Provide information on resources available for the core. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

Biographical Sketch Format Page (Administrative, Scientific, and ACE Funds Management Cores)

Do not repeat the biographical sketches of participating investigators since this information will be included at the end of the overall application (and therefore will be referenced in the Overall Table of Contents).

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide, with the following modification:

• For each core in the multi-project application, 3 publications plus other approved material are allowed.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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 Program 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 Program proposed).

• Is the Program as a whole scientifically compelling?
• Are the overall Program goals significant and focused on studies that meet the purpose and objectives of the FOA?
• Is the Research Agenda well described and substantial?
• Does the Agenda address important issues in understanding and/or treating human autoimmune diseases?
• Are the individual research projects and cores well coordinated and do they synergize towards achieving the central objectives of the Program?
• Will the integration of the individual projects into a single Program be more beneficial than pursuing each project independently?
• Is the proposed Collaborative Project a good candidate for contributing to the ACE Research Agenda?
• Do(es) the PD(s)/PI(s) have the leadership and scientific ability to develop an integrated and focused research Program?
• Is there adequate evidence of sufficient institutional support for the PDs/PI(s) in terms of laboratory space, equipment and other resources?
• For applications designated multiple PDs/PIs, is the Leadership Plan adequate and appropriate to ensure that there will be sufficient coordination and communication among the PDs/PIs?
• Is the Leadership Succession Plan adequate and feasible?
• Have the applicants and collaborators successfully developed and conducted collaborative research projects?
• Have the applicants and collaborators made a significant impact on the field of autoimmune diseases?
• For renewal applications, has substantial progress been made in the preceding period of support?

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 five scored 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? 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? Is the proposed pilot project innovative?

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?

Principal Project

• Does the Principal project address key aspects of the Center’s Research Agenda?
• Does it exploit the strengths of the applicants?

Pilot Project

• Does the Pilot project pursue an intriguing observation?
• Are the milestones well defined and appropriate?

Collaborative Project

• Does the proposed Collaborative Project have a good probability of establishing useful, productive collaborative investigation?
• Is there evidence of prior successful collaborative work?
• Does the Project answer broader questions beyond the abilities of a single Center?

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?

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the core 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 core proposed).

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the core 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 core proposed).

Administrative Core (required)

• Is the Staffing and Administrative Plan appropriate for the objectives of the proposed Program?
• Are the experience, level of commitment, and availability of the Core Leader adequate to manage the overall Program?
• Are the plans for coordination, problem identification and resolution and the establishment of a strong collaborative environment for the program appropriate?
• Are the proposed timelines, milestones and performance objectives for the overall Program adequate?
• Is the management plan for fiscal accountability and communication within the Program appropriate?

Scientific Core (if proposed)

• Is provision of resources and core services to the Research Projects justified?
• Is the relationship of the core to the central focus of the overall Program strong?
• Is the quality of the relevant facilities or services provided (including procedures, techniques, quality control) strong?
• Are the experience, level of commitment, and availability of the Core leader adequate to manage the overall Program?
• Are the criteria for prioritization and usage appropriate?
• Is the scientific core related to the theme of the overall Program?
• Is the justification provided that it will support at least 2 Research Projects adequate?
• Is the scientific core valuable to the overall ACE program?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed Program, Project or Core 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 Program, Project or Core 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.

Funds Management Core (if 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.

• Is the Staffing and Administrative Plan appropriate to manage the Program Funds?
• Are the experience, level of commitment, and availability of the Core Leader adequate?
• Are the plans for coordination, problem identification and resolution appropriate?
• Have adequate plans been made to receive, review, revise as needed, approve and implement budgets and execute contracts?
• Have adequate plans been made to receive, review, revise as needed, approve and pay invoices in a timely manner?
• Are the proposed timelines, milestones and performance objectives for the Fund Management Component suitable?
• Is the plan for fiscal accountability and communication within the Fund Management Component, with the Center, with the other ACEs, and with NIAID adequate?

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Allergy and Infectious Diseases Council. The following will be considered in making funding decisions:

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

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

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

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

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

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

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

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

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 NIAID reserves the right to terminate or curtail a study in the event of: (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other breach of the protocol; (b) substantive changes in the consensus protocol to which the NIAID does not agree; (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance; or (d) human subject ethical or safety issues that may dictate a premature termination.

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. The assigned program director may also serve as an NIH Project Scientist. The program official will monitor program progress, approve changes, and have access to data generated under these awards. NIAID staff may use the information for the preparation of internal reports on the activities of the group.

Program Director/Principal Investigator (PD/PI) Rights and Responsibilities

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

• Determining and coordinating the project activities scientifically and administratively;
• Participating actively in the formulation and implementation of the ACE Research Agenda;
• Setting project goals and timelines to achieve the proposed goals;
• Attending Steering Committee meetings, serving as a voting member of the Steering Committee, and accepting and implementing policies and procedures developed by the Steering Committee;
• Providing study data to the SACCC for management, quality control, and analysis;
• Submitting data to NIH-supported and/or public databases in accordance with policies agreed upon and established by the Steering Committee and the NIH data sharing policy available at: http://grants.nih.gov/grants/policy/data_sharing/ (see also Data Sharing below); and
• Participating in the cooperative nature of the group.

It is recognized that goals may require revision and re-negotiation during the course of the project period. Release of each funding increment by NIAID will be based on a review of progress towards achieving the previously agreed upon research goals. Awardees agree to accept close coordination, cooperation, and participation of the NIAID staff in those aspects of the scientific and technical management of the project described below.

Data Sharing

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. However, awardees should be committed to making the biological samples, diagnostic products, and other research tools, methods, data, and materials that are developed under the ACE awards available to other members of the ACE and to the research community. For data sharing information, see: NIH Data Sharing Policy.

Pilot Studies

The PD(s)/PI(s) will be responsible for ensuring that all pilot studies involving human or animal subjects have the appropriate clearances (i.e. IRB, FWA, IACUC, human subjects research training, and other required documentation) prior to implementation.

Intellectual Property

The awardee is solely responsible for the timely acquisition of all appropriate propriety rights, including intellectual property rights, and all materials needed for the awardee to perform the project.

Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any propriety rights, including intellectual property rights, or any materials needed by the awardee to perform the project.

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act). Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms.

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

• Provide advice and guidance on technical issues, such as reviewing progress.
• Assist the Steering Committee Chair and SACCC-ADCT in scheduling the meetings and teleconferences of the Steering Committee, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.
• Have access to data generated under this Cooperative Agreement. The information may be used by NIAID staff for the preparation of internal reports on the activities of the clinical trials/studies. Awardees will retain custody and rights to all data obtained with these awards.
• Provide assistance to the Steering Committee in the development of procedures for monitoring the performance of the clinical trials/studies.
• Provide and coordinate clinical data management and analysis, as needed.

NIAID will provide statistical, data management, and clinical trial operations support through a Statistical and Clinical Coordinating Center for Autoimmune Disease Clinical Trials (SACCC-ADCT) contract that is supported separately by NIAID. More information about this resource and other NIAID staff and contract responsibilities related to the support and conduct of ACE clinical trials may be found in the companion ACE, Clinical Program funding opportunity announcement.

A NIAID Representative will serve as a voting member of the Steering Committee.

Areas of Joint Responsibilities include:

Steering Committee

A Steering Committee will be established to direct the collaborative work of the ACE and determine the use of the Clinical Project Fund and Opportunity Fund. The PDs/PIs of the ACE basic and clinical awards, along with a representative of NIAID and a representative of the SACCC-ADCT, will be permanent, voting members of the Steering Committee. A Chair of the Steering Committee will be selected from among the PDs/PIs during the first meeting, a teleconference to be convened by the NIAID representative within a month of award. A plenary meeting will be held soon after award. All major scientific and budgetary decisions will be determined by the Steering Committee, with each member having one vote. An award with multiple PDs/PIs will share a single vote (a grantee with both clinical and basic awards has 2 votes). NIAID may appoint ad-hoc voting members to the ACE SC in order to provide scientific balance. To permit comprehensive reporting and discussion by the entire Committee, the formation of subcommittees and the delegation to them of discrete responsibilities and authorities is encouraged.

The Committee will meet twice each year in person and monthly by teleconference. Use of internet-enabled collaborative tools, including websites, email, conferencing, web logs (blogs), and community-moderated discussions are encouraged. A public website for the ACE (www.autoimmunitycenters.org) and a separate, password-protected secure site will be maintained by the SACCC-ADCT.

The Steering Committee will:

• Compose, approve, and post within 6 months of award on the public ACE website (www.autoimmunitycenters.org) an ACE Research Agenda for the entire program term. The Agenda will be based largely on the Clinical and Collaborative Projects but may include additional plans in order to foster collaborations among all of the members of the ACE. The Agenda include but is not limited to the following items;
  • Overall goals and Specific Aims,
  • Clinical and Collaborative Projects to be initiated within the coming year, and
  • Benchmarks and Timelines for accomplishing the work.
• Summarize and post on the public ACE website annual progress reports. For these annual public progress reports, each member of the ACE must summarize on 1 page their contribution to the ACE Research Agenda and progress from their individual institution, including any publications attributable to the ACE award.
• Review, prioritize, and schedule the full development and implementation of clinical trials and integrated mechanistic studies giving precedence when possible to the findings of peer review group;
• Coordinate completion and implementation of the Collaborative projects;
• Establish the goals, priorities and evaluation criteria for use of the ACE Clinical Project Fund and Opportunity Fund (administered by the Funds Management Component, to be awarded separately to a single ACE);
• Establish procedures for reporting results of ACE trials/studies (see below: Publication and Presentation of Findings from Clinical Trials/Studies);
• Promote collaborations among Clinical and Basic ACE programs;
• Assess pilot program progress at 18 months and review plans to extend the research or else replace the project

The clinical and research programs must be willing to work cooperatively and collaboratively both within their ACE and with other members. Clinical trials and mechanistic studies will proceed into the implementation stage only with the concurrence of the Steering Committee and the NIAID Project Scientist. The majority vote of the Steering Committee decides which group activities the Opportunity Fund will support.

Data Coordination and Management

Each awardee will be responsible for providing the NIAID with all study data for management, quality control and analysis, using procedures and standards determined by the Steering Committee. Specific analysis to be performed by NIAID will be directed by the Steering Committee or its designee. The awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS and NIH policies.

The Steering Committee will determine how data from multiple Centers collaborating on a study will be analyzed. Centers wishing to perform their own analysis of local data or of single site studies must obtain approval for the planned analysis from the Steering Committee.

Publication and Presentation of Findings from Clinical Trials, Mechanistic Studies, and Collaborative Projects

The Steering Committee will establish procedures for the publication and oral presentation of results or data collected within the ACE. The results of any collaborative work will be approved by the Steering Committee before it is made public. Publications and oral presentations of work performed under this agreement should acknowledge support by the Autoimmunity Centers of Excellence and NIAID.

Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. The members shall be: (1) one designee of the Steering Committee chosen without NIH staff voting, (2) one NIH designee, and (3) one designee with expertise in the relevant area who is chosen by the other two members. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

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

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

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: [email protected]

David Johnson, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-7104
Email: [email protected]

Paul Amstad, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-402-7098
Email: [email protected]

John A. Villella
National Institute of Allergy and Infectious Diseases (NIAID)
Phone: 301-451-2677
Email: [email protected]

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

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