Part I Overview Information

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Department of Health and Human Services

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

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

Title: Cooperative Centers for Translational Research on Human Immunology and Biodefense (U19)

Announcement Type
This is a reissue of RFA-AI-03-015.

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

• March 21, 2013 - This RFA has been reissued as RFA-AI-13-016.

Request For Applications (RFA) Number: RFA-AI-08-014

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

Key Dates
Release Date: February 29, 2008
Letters of Intent Receipt Date: June 18, 2008
Application Receipt Date: July 18, 2008
Peer Review Date: November, 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: April 2009
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/budget/qa/
Expiration Date: July 19, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Allergy and Infectious Diseases (NIAID) invites new or competing renewal applications from institutions with multi-disciplinary investigator teams to participate in the Cooperative Centers for Translational Research on Human Immunology and Biodefense (CCHI) program. The goal of this Funding Opportunity Announcement (FOA) is to support research on human immunology as it applies to potential agents of bioterrorism or emerging/re-emerging infectious diseases. The immediate objectives are to support basic and translational research on human immunological responses to NIAID Category A, B, or C Priority Pathogens, their toxins, or other emerging and re-emerging diseases (http://www3.niaid.nih.gov/research/topics/emerging/list.htm); and to create the stable, flexible, and centralized infrastructure needed to promote and coordinate multi-disciplinary research in human immunology as it relates to defense against these agents. This research program was originally established by NIAID in fiscal year 2003, and is now being renewed through open competition. All qualified investigators are invited to apply; prior funding under this program or through NIAID or NIH is not required.
• Mechanism of Support. This RFA will utilize the multi-project Cooperative Agreement (U19) grant mechanism.
• Funds Available and Anticipated Number of Awards. It is anticipated that approximately $25 million in total costs will be available in FY 2009 to support this program and that 7-9 awards will be made. An additional $1 million in total costs will be available per year in a Discretionary Fund to support Collaborative Resources that arise in the course of this program. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
• Budget and Project Period. The total project period for an application submitted in response to this FOA may not exceed five years. Applicants may request no more than $2 million direct costs per year. Note that consortium/contractual Facilities & Administrative costs are not factored into this direct cost limit. Such costs may be requested in addition to the $2 million direct cost limit.
• Renewal Applications. Competing renewal (type 2, formerly competing continuation ) applications will be accepted, as well as new (type 1) applications. At this time, it is not known if this FOA will be reissued.
• Resubmissions. Resubmissions will not be accepted for this FOA.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
• Number of Applications. A PD/PI may submit more than one application provided that each application is scientifically distinct. Furthermore, a PD/PI may serve as a Project Leader or Core Leader in another multi-project application under this FOA if there is no scientific overlap with the application submitted by the PD/PI.
• Number of PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be designated on the application. However, only one Project Leader or Core Leader may be designated for each project or core within the application, with the exception of the Administrative Core, in which the PD/PI(s) serves as the Core Leader(s).
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Initial merit review will be convened by the NIAID Division of Extramural Activities.

Table of Contents

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Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

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

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

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The long-term goal of the Cooperative Centers for Translational Research on Human Immunology and Biodefense (CCHI) program is the translation of research into clinical applications in humans. The immediate goals are to support basic and translational research on human immunological responses to NIAID Category A, B or C priority pathogens, their toxins, or other emerging or re-emerging infectious diseases (see list of eligible microorganisms at http://www3.niaid.nih.gov/research/topics/emerging/list.htm); and to maintain the stable, flexible, and centralized infrastructure needed to promote and coordinate multi-disciplinary research in human immunology as it relates to defense against these agents.

The CCHI program was originally established by NIAID in fiscal year 2003, and is now being renewed through open competition. All qualified investigators are invited to apply; prior funding under this program or through NIAID or NIH is not required.

The program is milestone-based and includes the flexibility to quickly redirect or replace research projects during the funding period. Funding beyond the first year will be contingent upon satisfactory progress in meeting negotiated milestones. Multi-investigator teams will be supported to conduct highly synergistic research with a scope of activities not possible with other funding mechanisms. Both basic and applied research topics are considered responsive. Although clinical research is the focus of this FOA, clinical trials are not allowed. The CCHI program places a major emphasis on infrastructure support to facilitate the translation from animal to human studies and to ultimately facilitate the translation of basic human research into clinical applications.

Applications may be submitted from single institutions or from consortia of institutions.

Background

The definitive study of immune response and regulation is much more difficult to achieve in humans than in animal model systems. Not only are experimental approaches limited, but genetic and environmental heterogeneity make it much more difficult to obtain reproducible data. Although many results from animal models do translate faithfully to humans, some clearly do not. Therefore, research must be conducted with human samples, to either verify findings from animal model systems or to discover and characterize the relevant human pathways. In addition, there is an ongoing need to develop new technologies that will facilitate studies in humans; for example, by minimizing sample sizes, allowing measurement of new parameters from readily obtainable samples, or imaging immune activity in situ by a variety of approaches.

Immune based defenses against agents of bioterrorism or emerging/re-emerging pathogens constitute very powerful weapons that complement drug-based approaches to control infectious disease. For example, the development of safe and effective vaccines will depend on better understanding of systemic and localized immune capacity, and of human variability at both the innate and adaptive levels of immunity and immunoregulation. Molecular mechanisms responsible for potent short-term immune responses and long-term immune memory must be understood and optimized for new applications. Immune-based reagents, such as antibodies or antimicrobial peptides, are needed for the passive protection of at-risk populations, and immune targets should be defined and tested to enhance immunomodulatory strategies.

In 2002, the NIAID convened a panel of expert scientists to identify research needs in the area of immunology and biodefense (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/biodimmunpan.htm) and established a Strategic Plan for Biodefense Research (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/strategic_plan.htm) as well as Research Agendas on Category A (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/biotresearchagenda.htm) and Category B and C (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/categorybandc.htm) Priority Pathogens. A 2007 update of the Strategic Plan (http://www3.niaid.nih.gov/topics/BiodefenseRelated/Biodefense/PDF/biosp2007.htm) was recently published, emphasizing the need to develop broad spectrum products with efficacy against a wide range or class of pathogens, to protect against the large number of potential threats. Such products might include novel diagnostics, immunomodulating agents, vaccine adjuvants, or cross-reactive or multiple-epitope vaccines. Broad spectrum technologies and platforms are also needed to support the development of common approaches useful for a number of different applications. Both basic and applied research activities will contribute to these objectives.

The CCHI program was established in 2003 as part of the overall NIAID biodefense effort. The renewal of this program will maintain NIAID’s commitment in this effort through continuing support for cooperative immunology centers focused on the translation of research from animals to humans.

Research Scope

All research activities must focus on human immunology and one or more of the NIAID Category A, B, or C Priority Pathogens, their toxins, or other emerging or re-emerging infectious diseases (see list at http://www3.niaid.nih.gov/research/topics/emerging/list.htm).

Each individual Research Project must include proposed studies on human cells or tissues.

Exclusions: The following research areas are excluded:

(1) clinical trials; i.e., clinical studies testing novel interventions in humans; however, the use of samples obtained from human subjects in clinical trials funded through independent mechanisms is allowed, as is the use of samples obtained from human subjects treated with licensed vaccines or drugs for the FDA approved purpose;

(2) HIV/AIDS;

(3) behavioral research; and

(4) epidemiological studies.

Applications proposing studies in the excluded areas will be considered non-responsive and will not be reviewed.

CCHI Program Components

Each CCHI application must include the three components described below: Research Projects, Technology Development Projects, and Core Activities. The allocation of dollars to each component within the requested budget is at the discretion of the applicant. Most emphasis should be placed on the Research Projects and the Technology Development Projects. It is expected that there will be a high level of synergy among the Research Projects.

1. Research Projects

Activities required: a minimum of three separate Research Projects, each led by a different Project Leader and focused on basic or applied immunology in the context of understanding, preventing, or treating Category A, B, or C Priority Pathogen infections or other emerging/re-emerging pathogen-mediated human diseases on the NIAID list. Each project should address a common immunological theme such that synergy is clearly evident among the projects.

Explicit, quantitative, yearly Milestones must be included in each project for assessing progress and success; these Milestones will be used by NIAID program staff in assessing progress and recommending continued funding on an annual basis.

Activities allowed: hypothesis-driven research, hypothesis-generating research, and/or descriptive or applied translational research on human immunology. Research topics may include, but are not limited to, the following areas:

• Molecular mechanisms of innate immunity;
• Innate immune receptors as targets for vaccine adjuvant development;
• Passive immunotherapy mediated by innate immune molecules, antibodies, or soluble receptors;
• Mechanisms of synergy and regulation at the innate-adaptive immune interface;
• Optimization of antimicrobial B and T cell effector mechanisms;
• Antigen processing and presentation to T cells;
• Antigen presenting cell functions;
• Mechanisms of mucosal immunity;
• Immunoregulation in the neonate or elderly;
• Generation and maintenance of B and T cell memory;
• Mechanisms of microbial immune evasion; and
• In vivo imaging of immune responses.

Animal studies are allowed, but only if their relevance to the human disease under study is clearly described in the application, and only if experimental approaches are described in the Research Plan and the Project Milestones for translating the results into studies on human cells or tissues within the five-year funding period.

Applicants are strongly encouraged to include both basic researchers and those with relevant clinical expertise as Project Leaders, and to establish close collaborations between the basic and clinical scientists. Applicants with no history of research on the NIAID Category A, B, or C agent(s) or other emerging/re-emerging agent(s) chosen for study are strongly encouraged to incorporate collaborators or consultants with documented expertise in the relevant research area. Inclusion of additional expertise, such as chemistry, physics, and bioinformatics, is also encouraged as warranted by the research topics.

Based on internal CCHI evaluations, as well as assessments by the CCHI Steering Committee (see below), replacement projects may be proposed at any time by the Project Director/Principal Investigator (PD/PI) for review and approval by the NIAID.

Activities not allowed: clinical trials (see above), HIV/AIDS research, behavioral research, epidemiological research, or animal studies that do not progress to human studies within the funding period.

2. Technology Development Projects

Activities required: a minimum of one and a maximum of three separate Technology Development Projects, each led by a different Project Leader and focused on the discovery, validation, development, and/or standardization of specialized assays or methods, novel reagents, or technologies that will be of use to the research community for studies on human immunology. The purpose of this component is to develop new resources for more definitive studies of human immunology. It is considered a research component and not a Core activity. The Project Leader(s) should have relevant documented expertise and sufficient effort dedicated to sustain a vigorous and productive effort. As provided for by NIH policy regarding the sharing of research resources (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm) new reagents, assays, methods, and technology protocols will be made publicly available. Scale-up plans for production and distribution of any new reagents should be included in the application.

The Technical Development Project(s) need not be related to the Research Projects and each must be capable of standing on its own scientific merit.

Explicit, quantitative, yearly Milestones should be included in each project for assessing progress and success; these Milestones will be used by NIAID program staff in assessing progress and recommending continued funding on an annual basis.

Activities allowed: research in the following areas, or in additional areas proposed by the applicant and appropriate to the goals of the CCHI program:

• Nano- or micro-assays that reduce required sample sizes;
• Single cell assay development;
• Development of new reagents;
• Techniques to improve high-throughput screening methods;
• Improved assays of immune effector function, such as antibody production or cytotoxic activity;
• Identification of biomarkers for specific immune responses;
• Improved characterization of dendritic cells or other antigen presenting cells; and
• In vivo imaging techniques for use in humans.

Based on internal CCHI evaluations, as well as assessments by the CCHI Steering Committee (see below), replacement projects may be proposed at any time by the PD/PI for review and approval by the NIAID.

Activities not allowed: provision of standard existing assays, methods, reagents, technologies, or other available research services. Such activities must be proposed as Scientific Cores (see below) if needed.

3. Core Activities

Requirement for each Core: a designated Core Leader is required for each proposed Core.

A. An Administrative Core is required and will be responsible for the overall organization, management, decision-making, and periodic evaluations within the individual Center; as well as data sharing, protection of intellectual property, and involvement of institutional resources. The PD/PI(s) of the application must serve as the Core Leader(s) of the Administrative Core.

This Core will: organize communications, group meetings, and teleconferences; organize the presentation and publication of data; allocate and re-allocate resources to meet program goals; prioritize fiscal and other resources; be responsible for resource sharing and transmission of information and reagents; manage the budget for program-related travel (including travel for the annual meetings see below); and identify and resolve problems and unexpected outcomes. This Core is also expected to create and implement administrative and leadership mechanisms that will foster effective interactions among the CCHI investigators and institutions to ensure a productive research effort.

In addition, the Administrative Core is required to support:

• An External Scientific Advisory Group (ESAG). The ESAG will be formed after award, and will evaluate scientific progress and provide advice to the individual Center on an annual basis. Specific potential members of the proposed ESAG should NOT be named in the application and ESAG candidates should NOT be recruited or even contacted prior to review and award. However, for renewal applications, any current or former ESAG members should be identified. The duties and responsibilities of the ESAG must be defined in the application. The budget request for the Administrative Core should include the costs for travel of the ESAG members to meet with CCHI personnel on an annual basis, and any additional meeting costs. A member of the CCHI program may not serve as an ESAG member for a different CCHI Center.
• An Education Program to support exchange of information on human immunology in the context of NIAID Category A, B, and C Priority Pathogens or other emerging/re-emerging infectious agents. Education activities may not include formal courses, and may not support the salaries or stipends of trainees. Education funds may not be used to purchase equipment, or to develop or distribute educational materials targeted to the non-scientific community. Education activities are restricted to support for:
  • Seminar series or symposia comprised of speakers from outside institutions to present research results on the human immunology of NIAID Category A, B, or C Priority Pathogens, or other emerging/re-emerging pathogens.
  • Practical, short-term training of laboratory staff, postdoctoral fellows, or other investigators, including personnel from outside of the Center, in the use of assays, methods, reagents, or technologies to study human immunology in the context of NIAID Category A, B, or C Priority Pathogens or other emerging/re-emerging pathogens.
  • Development of a Center website to provide scientific information to relevant research communities.

B. A Pilot Projects Core is required and will support small studies to generate preliminary data for the development and submission of future research applications for support from non-CCHI sources. Use of this Core should attract investigators new to the field of human immunology. Each Pilot Project supported by this Core will be of limited duration (up to two years) and of limited budget (up to $75,000 direct costs/year/project). The application must include a proposed plan delineating methods for tracking the success of the Pilot Projects program, by following the number of Pilot Projects that obtain subsequent independent funding and the publications that result from the Pilot Projects. Specific Pilot Projects will not be described within the application; only the process planned for support and management of the program will be described.

Applications must also include a plan that describes the process by which requests for Pilot Projects will be equitably solicited, reviewed, selected, and monitored within the Center for CCHI Steering Committee approval before actual implementation. The Steering Committee will conduct quarterly reviews of the Pilot Project applications for scientific excellence and programmatic relevance, and will approve funding of those applications deemed meritorious.

All Pilot Projects funded by CCHI awardees must focus on human immunology and Category A, B, or C Priority Pathogens, their toxins, or other emerging or re-emerging infectious diseases on the NIAID list. However, the topics need not be related to other research being conducted at the parent Center. Pilot Projects that support research by investigators outside of the parent CCHI group are encouraged and CCHI awardees will be especially encouraged to fund collaborations with other members of the CCHI network. Pilot Projects may also support research within the parent Center.

Activities not allowed within the Pilot Projects Core include equipment purchase and clinical trials (see above). In addition, support for a particular investigator, or for a particular project, is not allowed beyond a total of two years during the entire five year funding period. The annual direct costs for the entire Pilot Projects Core must not exceed $200,000 for all Pilot Projects.

C. Scientific Cores may be proposed, but only if they will be used by at least two of the Research and/or Technology Development Projects. Such Cores are limited to the provision of existing standard assays, reagents, technologies, or other available services to the CCHI investigators. Scientific Cores must be well justified and clearly non-duplicative of other services or facilities available to the CCHI investigators. If modified or replacement Research and/or Technology Development Projects significantly change the use of such Cores during the funding period, funds may be re-budgeted within the CCHI after approval by NIAID. Scientific Cores may include clinical, statistical, technical (e.g., flow cytometry, proteomics), informatics, or other non-administrative activities that directly support the research program.

If appropriate to the particular CCHI, repositories for cells, tissues, reagents, or large data sets may be funded as Scientific Core activities. In this case, applications should include methods to obtain, protect, and archive relevant clinical and/or family history information. In addition, appropriate informatics capability should be provided to track data and link to other data sets. A plan for the distribution of samples, reagents, data, and other resources should be included and conform to the NIH policies on data and resource sharing (see Section III.6. Other Submission Requirements).

Applications proposing Scientific Cores must indicate the specific projects to be served by that Core and explain why those Core resources are not otherwise available at the applicant institution or through other grant mechanisms, for example NIH-funded centers programs or clinical networks. The apportionment of dollars, or percentage of dollars, that will be required to support each component Research or Technology Development Project that will utilize each Scientific Core should also be presented.

CCHI Steering Committee

A Steering Committee will serve as the governing board of this collaborative research program; its actions and decisions will be determined by majority vote. Voting membership will include one PD/PI from each CCHI. The NIH Project Scientist will serve as a non-voting member. Steering Committee responsibilities are further described under Section VI.2.A.3. Cooperative Agreement Terms and Conditions of Award Collaborative Responsibilities.

Cooperative Resources/Discretionary Funds

NIAID plans to set aside approximately $1 million per year in Discretionary Funds to support Cooperative Resources that provide central assistance and technical expertise for projects undertaken by CCHI investigators. Examples of possible Cooperative Resources include genomic/proteomic, imaging, or sophisticated flow cytometry facilities. The CCHI Steering Committee will establish the goals, priorities, and evaluation criteria for the use of the Discretionary Funds to establish Cooperative Resources. PD/PI(s) awarded under this FOA will have an opportunity to compete for the Discretionary Funds and will be provided with details regarding Discretionary Fund management and the application process. Allocations from the Discretionary Fund must be approved by majority vote of the CCHI Steering Committee. Scientific Cores funded within individual Centers may be expanded to become Cooperative Resources using these Discretionary Funds upon approval by the CCHI Steering Committee. Cooperative Resources may be housed at particular Centers or may be supported through subcontracts to other facilities.

After award, one awardee institution will be selected by the NIAID to manage the Discretionary Funds for the entire program. See Section VI.2.A.3 Collaborative Responsibilities for further information on the Discretionary Fund.

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the multi-project U19 Cooperative Agreement award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

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

The NIH U19 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PD/PI, as described in Section VI.2.Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award.

At this time, NIAID has not determined whether and how this solicitation will be continued beyond the present FOA.

2. Funds Available

The NIAID intends to commit approximately $25 million in FY2009 to fund 7-9 new and/or competing renewal applications in response to this FOA. In addition, approximately $1 million per year will be allocated in a Discretionary Fund to support Collaborative Resources that arise in the course of this program.

The total project period for an application submitted in response to this funding opportunity may not exceed 5 years. Although the size of award may vary with the scope of research proposed, applicants may request no more than $2 million direct costs per year.

Funds may not be used for renovations or alterations.

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

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

1.B. Eligible Individuals

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

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for programs that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research awards can be found at http://grants.nih.gov/grants/multi_pi.

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

Note that multiple Project Leaders or Core Leaders are not allowed for individual Research Projects, Technology Development Projects, the Pilot Project Core, or the Scientific Cores. The Core Leader(s) of the Administrative Core will be the PD/PI(s) of the overall application.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

• A PD/PI may submit more than one application provided that each application is scientifically distinct. Furthermore, a PD/PI may serve as a Project Leader or Core Leader in another multi-project application under this FOA if there is no scientific overlap with the application submitted by the PD/PI.
• The PD/PI is expected to commit substantial time and effort to ensure success of the program.
• Renewal applications will be permitted for this FOA.
• Resubmission applications will not be accepted.
• Applications may be submitted from single institutions or consortia of institutions.

Section IV. Application and Submission Information

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1. Address to Request Application Information

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

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

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

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

Applications from foreign organizations must:

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

In addition, for applications from foreign organizations:

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

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

Applications with Multiple PDs/PIs

Projects using the multiple PD/PI(s) plan should include a cover letter stating explicitly that the multiple PD/PI(s) approach is being undertaken for the application. The letter should include the names and institutional information for each PD/PI and the appropriate institutional business office contact information plus the name of the business official authorized to sign grant applications.

Whenever multiple PDs/PIs are proposed NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The Contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above. The Contact PI may be changed during the project period.

Multiple PD/PI Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions for non-modular budget preparation.

Multiple PD/PI Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the non-modular budget component. All other institutions should have their individual budgets attached separately to the non-modular budget component of the prime institution.

Supplemental Instructions for the Preparation of Multi-project Applications

The following section supplements the instructions found in the PHS Form 398 for preparing multi-project grant applications that will be submitted in paper format. Additional instructions are required because the PHS Form 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 supplemental instructions below are divided as follows:

A. General Instructions addresses collaborative efforts among research projects, the administrative and organizational structure, as well as the overall facilities and environment, and the overall budget.

B. Specific Instructions for Individual Projects describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

C. Specific Instructions for Core Units Cores must provide services or resources to support at least two projects. Instructions describe modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of the project.

A. General Instructions

All applications must be submitted on PHS Form 398. The multi-project grant application should be assembled and paginated as one complete document.

Note that pages in excess of the allowed limits will be removed from the application and will not be reviewed.

The order of presentation should be as follows:

• Form pages and composite budget as described below
• Program Overview (25 page limit)
• Leadership Plan for Multiple PDs/PIs (3 page limit)
• Research Project 1 (research plan: 25 page limit)
• Research Project 2 (research plan: 25 page limit)
• Research Project 3 (research plan: 25 page limit)
• Research Project 4-n (optional; research plan: 25 page limit each)
• Technology Development Project 1 (research plan: 25 page limit)
• Technology Development Project 2-3 (optional; research plan: 25 page limit each)
• Core A: Administrative Core (research plan: 10 page limit)
• Core B: Pilot Projects Core (research plan: 5 page limit)
• Core C-n: Scientific Core(s) (optional; research plan: 10 page limit each)
• Biographical Sketches
• Checklist
• Appendix

1. Form Page 1 - Face Page

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

When multiple PDs/PIs are proposed, use the Face Page-Continued page to provide items 3a-3h for all PDs/PIs. The Contact PI should be listed on block 3 of Form Page 1-Face Page, with additional PDs/PIs listed on the Face Page-Continued. All PDs/PIs must be registered in the eRA Commons prior to the submission of the application.

2. Form Page 2

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

List the performance sites where the research will be conducted.

Under "Key Personnel", list the PD/PI(s) of the multi-project application, followed by the Leaders of the component projects and cores, other key personnel, and then other significant contributors.

When multiple PDs/PIs are proposed, list the Contact PI first, then all additional PDs/PIs in alphabetical order. Then list all Key Personnel, giving name and organization.

3. Form Page 3 - Table of Contents

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 project by project 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 project and core. A page reference should be included for the budget for each project and each core. Further, each research project and technology development project should be identified by number (e.g., Project 1), title, and responsible Project Leader, and each Core should be identified by letter (e.g., Core A), title, and responsible Core Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4. Composite Budget

Do not use Form Page 4 of the PHS 398. Instead, using the suggested format presented below, prepare a composite budget for all proposed years of support. (Justification for budget elements should not be presented here but in the individual budgets of the projects and cores.)

SAMPLE: Consolidated Direct Cost Budget for All Proposed Years of Support

Component	Year 1	Year 2	Year 3	Year 4	Year 5	All Years
Project 1. Invest.	125,000	130,000	135,200	140,608	146,232	677,040
Project 2. Study	125,000	130,000	135,200	140,608	146,232	677,040
Project 3. Develop.	100,000	104,000	108,160	112,486	116,985	541,631
Core A. Admin. Core.	50,000	52,000	54,080	56,243	58,493	270,816
Core B. DNA	25,000	50,000	52,000	54,080	56,243	237,323
Totals	425,000	466,000	484,640	504,025	524,185	2,403,850

5. Form Page 5

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry.

6. Biographical Sketch Format Page

Biographical sketches of all professional personnel for all components should be placed at the end of the application with the PD/PI(s) first, followed by those of other key personnel in alphabetical order.

7. Other Support Format Page

Do not complete. (Any required information will be requested from successful applicants prior to grant award.)

8. Resources Format Page

Do not complete. Essential information is to be presented in the individual research and/or technical development project and core sections of the application.

9. Program Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-project application and is limited to 25 pages. 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. The synergies to be achieved through the establishment of multi-disciplinary teams and novel collaborations should be fully described. The Technical Development Project(s) need not be related to the Research Projects and each must be capable of standing on its own scientific merit.

The Overview provides an introduction to the proposed research, outlines the specific questions to be explored, describes the key preliminary data supporting the experimental approach, and addresses the synergy of the individual Research Projects, the promise of the Technology Development Project(s), and the processes and procedures that will be developed and utilized to administer the program.

This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by providing an overview of the general problem area and by laying out a broad strategy for attacking the problem. As the strategy develops, each Project and Core should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique.

If the application is a renewal of a prior Cooperative Centers for Translational Research on Human Immunology and Biodefense grant, this section should also highlight the major accomplishments from the prior funding period. In addition to discussing results from individual projects, describe the synergy and collaborations that occurred. Other points to include are: which institutions were part of the prior CCHI; the numbers and quality of publications; any patents filed; researchers brought into the study of human immunology or into biodefense research; and how the CCHI was managed.

10. Leadership Plan for Multiple PDs/PIs

For applications designating multiple PDs/PIs, a Leadership Plan must be included and is limited to 3 pages (see Section I of the PHS 398 Research Plan for additional guidance). The use of this option must comply with the requirements described in http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-017.html. The governance and organizational structure of the leadership team and the overall CCHI should be described, including communication plans, process for making decisions on scientific direction, intellectual property issues, and procedures for resolving conflicts. The roles and shared administrative, technical, and scientific responsibilities for the program should be delineated for the PDs/PIs and other collaborators, including responsibilities for human subjects and animal studies as appropriate.

11. Checklist

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

12. Appendix

A change in policy limiting Appendix materials began with receipt dates on or after January 3, 2007 (NOT-OD-07-018). http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

For each project or core in the multi-project application, 3 publications plus other approved material are allowed. The Appendix may not be used to circumvent the page limitations of the Research Plan. The Appendix material should be collated as one body of material and submitted on CD only, as indicated below. at the end of the application with eEach document file must include header information clearly labeledindicating the referring to the project or core to which it applies.

• Publications No longer allowed as appendix material except in the circumstances noted below. Applicants may submit up to 3 of the following types of publications in PDF format only:
• Manuscripts and/or abstracts accepted for publication but not yet published: The entire article should be submitted and may be stapled..
• Manuscripts and/or abstracts published, but a free, online, publicly available journal link is not available: The entire article should be submitted and may be stapled.
• Patents directly relevant to the project: The entire document should be submitted and may be stapled.

(Do not include unpublished theses, or abstracts/manuscripts submitted (but not yet accepted) for publication.)

Note: Publications and/or abstracts in press should no longer be included in the appendix material. Include the URL or PMC submission identification numbers along with the full reference in the Literature Cited section, the Progress Report for Competing Renewals section, and/or the Biographical Sketch section.

• Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents. These may be stapled as sets.
• Original glossy photographs or cColor images of gels, micrographs, etc., provided that a photocopy (may be reduced in size) is also included within the 25-page limit of Items a-d of the research plan. No photographs or color images may be included in the Appendix that are not also represented within the Research Plan.

Beginning May 25, 2008 and for all subsequent due dates, all paper PHS 398 applications must provide appendix material on CD only, and include five (5) identical CDs in the same package with the application. (See NOT-OD-08-031; http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html) Paper applications submitted for due dates prior to May 25, 2008 may voluntarily provide the appendix on five identical CDs; if submitting CDs it is not necessary to include a paper appendix.

Please note that a summary listing of the items included in the appendix is encouraged but not required. When including a summary it should be the first file on the CD.

When preparing CDs:

• Use PDF format. Where possible, applicants should avoid creating PDF files from scanned documents. NIH recommends producing the documents electronically using text or work-processing software and then converting to PDF. Scanned documents are generally of poor quality and difficult to read.
• Label each disk with the PD/PI name and application title.
• If burning CD-ROM disks on a Mac, select the ISO 9660 format.
• Do not use compression techniques for the electronic files.
• Do not use password protection, encryption, digital signature and/or digital certification in the PDF files.

Appendix materials may be submitted in paper format; five collated sets are needed. Applicants are encouraged to send Appendix materials on a CD in PDF format in lieu of the five collated sets. See application instructions for details on preparing CDs. Only a single CD need be sent.

For materials that cannot be submitted electronically or materials that cannot be converted to PDF format; (e.g., medical devices, prototypes, DVDs, CDs), applicants should contact the Scientific Review Officer (SRO) for instructions following notification of assignment of the application to a study section. If the SRO is listed in the FOA, he/she should be contacted in advance to address acceptability of materials.

B. Specific Instructions for Individual Research Projects and Technology Development Projects

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each project.

Each Project application must include: a cover page; PHS Form Page 2; Budget pages (PHS Form Pages 4 and 5); with budget justifications; Items 2-5 of the Research Plan as defined in the PHS 398 instructions; Proposed Yearly Milestones; Protection of Human Subjects from Research Risks; Vertebrate Animals; Select Agent Research/Biohazards; and Literature Cited.

1. Cover Page

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

Project Number and Title: (e.g., 1. Mechanisms of Immune Response to Ebola Virus in Humans)

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

Human Subjects: (Yes or No)

If Yes, exemption number:

(or)

IRB Approval Date: (e.g., 12/13/2006,or Pending)

(and)

Federalwide Assurance (FWA) number:

Vertebrate Animals: (Yes or No)

If Yes, IACUC Approval Date: (e.g., 11/17/2006, or Pending)

(and)

Animal welfare assurance number:

Proposed Period of Support:

From: (mmddyy - e.g., 07/01/2007)

To: (mmddyy - e.g., 06/30/2112)

Costs Requested for Initial Budget Period: (e.g. 07/01/2007-06/30/2008)

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

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

Costs Requested for the Entire Budget Period: (e.g., 07/01/2007-06/30/2112)

Direct Costs: (e.g., $700,000)

Total Costs: (e.g., $1,000,000)

Applicant Organization:

(full address)

2. Form Page 2

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

List the performance sites where the research will be conducted.

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

3. Form Page 3

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

4. Biographical Sketches

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).

5. Research Plan (Items 2-5 cannot exceed 25 pages)

6. Proposed Yearly Milestones

Within 2 pages maximum (these pages do not count against the 25 page limit for sections A-D of the Research Plan), describe specific, quantitative Milestones that should be achieved in each year of the Project. These Milestones will not be scored by the peer review panel and are subject to negotiation with the NIH Program Officer post-award.

7. Appendix: Do not create a separate appendix for an individual project. All appendix material should be collated as one body of material as described above.

D. Specific Instructions for Cores

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each proposed core.

1. Cover Page

The Face Page of the PHS 398 Form should not be used as a cover page for cores within a multi-project application. Instead, use the PHS 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 (these are a subset of the information provided on a PHS 398 Face Page:

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., 5/14/06, or Pending)

(and)

Federalwide Assurance (FWA) number

Vertebrate Animals (Yes or No)

If Yes, IACUC Approval Date (e.g., 4/15/07, or Pending)

(and) Animal welfare assurance number

Proposed Period of Support

From: (mmddyy, e.g., 07/01/2007)

To: (mmddyy, e.g., 06/30/2012)

Costs Requested for Initial Budget Period

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

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

Costs Requested for the Entire Budget Period

(e.g., Direct Costs: $212,323)

(e.g., Total Costs: $297,252)

Applicant Organization

(full address)

2. Form Page 2

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 multi-project program objectives.

List the performance sites where the core activities and services will be conducted.

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

3. Form Page 3

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

4. Biographical Sketches

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

5. Core Research Plan (Items 2-5 cannot exceed 10 pages for the Administrative Core, 5 pages for the Pilot Projects Core, and 10 pages for each Scientific Core)

6. Appendix: Do not create a separate appendix for an individual Core. All appendix material should be collated as one body of material as described above.

3. Submission Dates and Times

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

3.A. Receipt, Review, and Anticipated Start Dates
Letters of Intent Receipt Date: June 18, 2008
Application Receipt Date: July 18, 2008
Peer Review Date: November 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: April 2009

3.A.1. Letter of Intent

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

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

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

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-435-9369; 301-496-2550
FAX: 301-480-2310
Email: pm158b@nih.gov

3.B. Sending an Application to the NIH

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

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

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

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

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-435-9369; 301-496-2550
FAX: 301-480-2310
Email: pm158b@nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NIAID. Incomplete and non-responsive applications will not be reviewed.

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

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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

6. Other Submission Requirements

Special requirements of this FOA include:

• A minimum of three individual synergistic Research Projects organized around a central scientific theme
• A minimum of one and a maximum of three Technology Development Project(s)
• An Administrative Core that includes a required (to be named) External Scientific Advisory Group and an Education Program
• A Pilot Projects Core

Applications will be considered non-responsive and will not be reviewed if any of the above components are not included in the application or if each proposed Research Project does not focus on human immunology and Category A, B, or C Priority Pathogens, their toxins, or emerging or re-emerging infectious diseases on the NIAID list (http://www3.niaid.nih.gov/research/topics/emerging/list.htm).

Applications will not be eligible for funding if reviewers recommend removing projects from the program such that fewer than three Research Projects, or fewer than one Technology Development Project, remain.

DOCUMENTATION ON THE USE OF HUMAN SPECIMENS

All applications will involve the use of human samples. Such samples may be derived from tissue banks, repositories, clinical studies, or independently-funded clinical trials that are planned, ongoing or completed. Depending on the origin of the human specimens used in the proposed studies, applications should include as appropriate:

For each individual Project or Core involving human specimens:

(1) Documentation of the ability to acquire human samples, including written agreements between the PD/PI and the applicant institution, a clinical trial sponsor(s), including drug companies, if applicable, and an IND sponsor, if not one of the above, for the conduct of a study from which samples will be obtained.

(2) A draft consent form, when necessary, to obtain human samples not provided for in an associated clinical trial/study.

(3) A detailed description of any proposed clinical study, including: hypothesis, study objectives, study population, relevance of the proposed study to clinical disease/patient outcome, statistical design and analysis plan, plan for management and quality control of data, and plan for receipt and storage of human samples.

Resource Sharing Plan(s)

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

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

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

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

Specific Instructions for Foreign Applications

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

Section V. Application Review Information

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1. Criteria

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

The following will be considered in making funding decisions:

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

2. Review and Selection Process

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

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

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Allergy and Infectious Diseases Council.

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

Review Criteria for the Overall Application

The following items will be considered in the determination of overall scientific merit and priority score for the entire application:

Overall score: a single numerical priority score will be assigned to the whole application after consideration of all of the elements. The overall score for the application will be based primarily on the scientific merit of the individual components, with additional consideration of the overall synergy of the Research Projects, integration of all the components, the overall program organization, and the capabilities of the associated personnel. The overall score will depend on the perceived ability of the proposed work to advance knowledge of human immunology in general and as it applies to countering potential agents of bioterrorism and emerging infectious diseases. The clarity and completeness of the application’s combined components with regard to specific goals, proposed feasibility, and progress towards stated goals are critical.

If peer reviewers deem that fewer than the required three Research Projects, or fewer than the required one Technical Development Project, have substantial and significant merit, the entire application is not recommended for further consideration (NRFC).

Review criteria for the overall application:

• Scientific merit of the program as a whole, as well as that of the individual Research Projects, Technology Development Project(s), Scientific Core(s), Pilot Projects Core, and Administrative Core including the Education Program.
• Adequacy and significance of the human immunology focus and potential application to biodefense or emerging/re-emerging infectious disease issues.
• Adequacy and appropriateness of the plans to establish, coordinate, and manage a synergistic research program to achieve the goals of the CCHI, including plans for equitable resolution of conflicts and decision-making.
• Integration: the scientific gain achieved by combining the component Research Projects into a multi-project program beyond that achievable if each project were to be pursued independently (synergy).
• Leadership and scientific ability of the PD/PI to develop an integrated, multi-disciplinary program with a well-defined central research focus, and commitment and ability to devote adequate time and effort to the program. Although the scientific merit of the U19 is based on the overall quality and rated projects and cores, any components NRFC are considered in the peer review evaluation of the PD/PI’s leadership and program administration skills.
• For applications designating multiple PDs/PIs, appropriateness and adequacy of the Leadership Plan to ensure that there will be sufficient coordination and communication among the PDs/PIs; appropriateness of the administrative plans for the management of the projects, including plans for resolving conflicts.
• Qualifications, experience, and commitment of investigators responsible for the individual research projects and cores and their contribution to the program, including their ability to devote time and effort to the program.
• For renewal applications, accomplishments achieved during the prior funding period.

Review Criteria for Individual Research Projects and Technology Development Projects

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

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

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

Investigators: Are the Project Leader and other key investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Project Leader and other researchers? Do the Project Leader and the investigative team bring complementary and integrated expertise to the project?

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

NOTE: Synergy and thematic relatedness between the projects, and their significance for the program as a whole, are not discussed when rating individual projects. These characteristics are discussed and rated under the Integration review criterion when evaluating the Overall Program.

Review Criteria for Cores

Administrative Core

• Is the administrative and organizational structure appropriate and sound to facilitate attainment of the objective(s) of the proposed program?
• Is the management plan for fiscal accountability and communications within the overall program appropriate?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Is the experience, level of commitment, and availability of the Administrative Core Leader(s) and administrative staff adequate to manage the overall program?
• Are the plans to utilize the External Scientific Advisory Group adequate?
• Is the Education Program adequate to support exchange of information on human immunology in the context of NIAID Category A, B, and C Priority Pathogens, their toxins, or other emerging/re-emerging infectious diseases on the NIAID list?

Pilot Project Core

• Is the experience, level of commitment, and availability of the Pilot Projects Core Leader and staff adequate to manage the pilot program?
• Are the plans for solicitation, review, administration, evaluation, and fiscal accountability of pilot funds appropriate and sound?
• Are there adequate plans to track outcomes of Pilot Project support?

Scientific Cores (if proposed)

• Are the justification and usefulness of the core facilities to the individual Research Projects or Technology Development Project(s) appropriate and sound?
• Is the relationship of each core to the central focus of the overall program strong?
• Are the quality of the relevant facilities or services provided (including procedures, techniques, and quality control) and criteria for prioritization and usage appropriate?
• Are the qualifications, competence, and commitment of the Scientific Core Leader and key personnel appropriate?

2.A. Additional Review Criteria:

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

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

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

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

Select Agent Research/Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate (see the Research Plan, Section G on Select Agent Research in the PHS Form 398).

2.B. Additional Review Considerations

Milestones: The adequacy and appropriateness of the yearly Milestones for each of the Research Projects and the Technology Development Project(s). The evaluation of the Milestones will not be factored into determining the overall priority score.

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

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

• Data Sharing Plan. [http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm]
• Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

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1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page).

Effective January 1, 2008, NIH will no longer provide paper notification of the Notice of Award (NoA) letters. Instead, NoAs will be sent solely via e-mail to grantee organizations and will be accessible in the eRA Commons through the Status module. All award recipients are required to be e-mail enabled to allow for the electronic transmission of the NoA. Institutions registered in the Commons should verify the e-mail address on file is correct, or add the appropriate e-mail address. For more information regarding this requirement, please read the NIH Guide Notice, NOT-OD-08-002, http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-08-002.html.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

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

The following terms and conditions will be incorporated into the NoA and will be provided to the PD/PI and the appropriate institutional official at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility reside with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Project Director/Principal Investigator (PD/PI) Rights and Responsibilities

The PD/PI will have the primary responsibility for: defining the research plan and goals; overseeing/performing the scientific activities of the plan; ensuring successful completion of Milestones within the timeframe and budget proposed; cooperating with NIAID programmatic, technical, and administrative staff; and administratively managing the U19. One PD/PI from each CCHI will be a voting member of the CCHI Steering Committee (see below), will participate in all Steering Committee activities, and will follow the policies and procedures developed by the Steering Committee. Awardees must be committed to making research samples and tools, methods, data, and materials that they develop under this program available to other members of this program as well as the research community, subject to the rights described below.

Monitoring Clinical Studies

NIH policy requires that clinical studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. An updated NIAID policy was published in the NIH Guide on July 8, 2002 and is available at http://grants.nih.gov/grants/guide/notice-files/NOT-AI-02-032.html. The full policy, including terms and conditions of award, is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

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

1. Each institution engaged in human subjects research has a current, approved Assurance Number on file with the DHHS Office for Human Research Protections (OHRP).
2. Each protocol and informed consent document is approved by the responsible Insitutional Review Board (IRB)/Ethics Committee (EC) prior to subject entry.
3. For Investigational New Drug (IND) studies, each local Investigator of Record has supplied a completed FDA Form 1572 to NIAID for each protocol conducted at each site. INDs may be held by the PD/PI, by a commercial subcontractor, or by the NIAID.
4. Each study investigator and sub-investigator has provided current curriculum vitae to NIAID.
5. Each study participant (or legal representative) will sign an IRB/EC-approved protocol consent prior to entry on study as part of the Informed Consent Process.
6. All clinical research activities performed outside of the U.S. must, in addition to U.S. Federal regulations, comply with the host country regulations for human subjects.

Milestones

The applicants will describe yearly Milestones for each Research Project and Technology Development Project of the proposed CCHI. It is recognized that Milestones may require revision and re-negotiation during the course of the project period. The NIH Program Official will negotiate the Milestones with the PD/PI(s) and provide approvals. Release of each yearly funding increment by NIAID will be based on a NIAID review of progress towards achieving the previously agreed upon Milestones.

External Scientific Advisory Group

After award, the PD/PI will establish an External Scientific Advisory Group (ESAG) comprised of three to four investigators outside of the overall CCHI program. The ESAG will meet annually with the Center personnel to evaluate progress and provide advice on future directions. Costs will be borne by the awardee.

Pilot Studies

The PD/PI 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 in domestic and foreign institutions) prior to implementation. The PD/PI must inform the NIH of any awards made for pilot studies involving foreign sites prior to their initiation. Pilot studies involving foreign sites cannot be initiated without first obtaining NIH clearance and approvals for protection of human subjects and animals, including specimens.

Site Visits

The PD/PI will host site visits by NIAID program staff as requested by the program staff. These site visits may be held in conjunction with meetings of the CCHI members with their ESAG.

Intellectual Property

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

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

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 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.

Highly Pathogenic Agents and/or Select Agents or Toxins (Agents)

The research proposed in this grant may involve Select Agents and/or Highly Pathogenic Agents.

NIAID defines a Highly Pathogenic Agent as an Infectious Agent or Toxin that, under some circumstances, may warrant a biocontainment safety level of BSL3 or higher according to any one of the following sources:

• The current edition of the CDC/NIH Biosafety in Microbial and Biomedical Laboratories (BMBL) (http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm),
• Your Institutional Biosafety Committee (IBC) or equivalent body, and
• An appropriate designated institutional biosafety official.

If there is ambiguity in the BMBL guidelines and/or there is disagreement among the BMBL, an institutional committee, or institutional official, the highest recommended containment level must be used.

At the beginning of each Progress Report clearly indicate:

Whether or not any research with a Highly Pathogenic Agent or Select Agent has been performed or is planned to be performed under this grant.

If yes, describe if your IBC or equivalent body or official has determined, for example, by conducting a risk assessment, that the work being planned or performed under this grant may be conducted at a biocontainment safety level that is lower than BSL3.

If the work involves Select Agents and/or Highly Pathogenic Agents, also address the following points:

Any changes in the use of the Agent(s) or Toxin(s) that have resulted in a change in the required biocontainment level, and any resultant change in location, if applicable, as determined by your IBC or equivalent body or official.

If work with a new or additional Agent(s)/Toxin(s) is proposed in the upcoming project period, provide:

• A list of the new and/or additional Agent(s) that will be studied;
• A description of the work that will be done with the Agent(s);
• The title and location for each biocontainment resource/facility, including the name of the organization that operates the facility, and the biocontainment level at which the work will be conducted, with documentation of approval by your IBC or equivalent body or official. It is important to note if the work is being done in a new location.

For domestic work with Select Agents provide documentation of Registration status of all domestic organizations/entities where Select Agents(s) will be used.

Please be advised that changes in the use of a Select Agent not previously described in the original application or last progress report will likely be considered a change in scope and, therefore, require NIH awarding office prior approval.

Publications

The PD/PI will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by members of the grant and supported in part or in total under this Agreement. The PD/PI and Project Leaders are requested to submit manuscripts to the Program Officer within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained and joint press conferences and press releases prepared. Publications or oral presentations of work performed under this Agreement are the responsibility of the PD/PI and appropriate Project Leaders and will require appropriate acknowledgement of NIAID support. Timely publication of major findings is encouraged.

Discretionary Fund Management

One awardee institution will be selected by NIAID after award to administer the Discretionary Fund. This institution must agree to take responsibility for managing the funds, including the disbursement, administration, and reporting on the use of discretionary funds as approved by the Steering Committee.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

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

A program official from the NIAID Division of Allergy, Immunology, and Transplantation (DAIT) will serve as the NIH Project Scientist for this program. In conjunction with other NIAID scientific program staff and the CCHI Steering Committee (see below), the NIH Project Scientist will provide advice and guidance on technical issues, such as reviewing progress or recommending changes. Administrative assistance will be provided by the NIH Project Scientist in conjunction with the NIAID Grants Management Office. The NIH Project Scientist may also: provide input into the design of activities; advise in the selection of sources or resources (e.g., determining where a particular reagent may be found); coordinate or participate in the collection and/or analysis of data; or advise in the management and technical performance.

The NIH Project Scientist will serve as a non-voting member of the Steering Committee, schedule the meetings and teleconferences of the Steering Committee, and ensure coordination of Steering Committee activities and implementation of its recommendations, decisions, and policies.

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 Notice of Grant Award. The assigned Program Official may also serve as the Project Scientist.

2.A.3. Collaborative Responsibilities

CCHI Steering Committee

A Steering Committee will be established to serve as the governing board of the CCHI program. The Committee will be comprised of the PD/PI of each U19 grant and the NIAID Project Scientist, and may also include other individuals with expertise in the scientific areas, as well as Program Officials from the NIAID Division of Microbiology and Infectious Diseases. Only one PD/PI from each U19 grant and the NIAID Project Scientist will be voting members of the Steering Committee and each will have one vote. The NIAID Project Scientist will serve as a non-voting member of the Steering Committee. Awardees will be required to accept and implement policies approved by the Steering Committee.

The CCHI Steering Committee will meet quarterly by teleconference, except for one yearly face-to-face meeting in conjunction with the annual Scientific Meeting (see below). A Steering Committee Chair will be elected by majority vote from among the U19 PD/PIs at the first Steering Committee meeting.

The responsibilities of the CCHI Steering Committee will be to:

• Evaluate progress of the U19 projects and provide guidance;
• Review and approve Pilot Projects proposed by the PDs/PIs, quarterly;
• Establish protocols for the review and modification of ongoing studies, which may include modification of project Milestones and recommendations for new collaborations and resource allocations among the program members;
• Assist, as required, in preparing formal reports summarizing activities and/or progress;
• Ensure the timely release of data to NIH-supported and/or public databases; and
• Determine and coordinate the use of Cooperative Resources (see below) by the program members, including reagents, samples, and services.

NIAID intends to support the peer-reviewed studies proposed in the awarded grant applications. However, under special circumstances, the Steering Committee will establish guidelines and review procedures to evaluate and determine opportunities for redirection or modification of the peer-reviewed projects. This policy is in keeping with the terms and conditions of the cooperative agreement mechanism.

Scientific Meetings

All awardees will participate together in an initial meeting, arranged by the NIAID Project Scientist, to be held soon after award in the Bethesda, MD area; and will participate in face-to-face scientific meetings of all PDs/PIs to be held annually thereafter. Quarterly teleconferences of the Steering Committee will also be held. All PDs/PIs are required to attend these meetings, together with additional scientific staff from their CCHI when appropriate. The scientific meetings are open to members of the CCHI program and to NIH extramural staff, and will serve as opportunities for members to provide the latest update on their research, exchange ideas and information, and discuss collaborations among program members. Meeting participants will identify the group’s tangible resources, capabilities, and needs to advance overall program goals. The PDs/PIs are required to give oral presentations at the annual meetings on current and planned activities and projects.

Cooperative Resources/Discretionary Funds

The CCHI Steering Committee may establish and support Cooperative Resources that provide central assistance and technical expertise for projects undertaken by CCHI investigators under this program. NIAID Discretionary Funds will be available to the Steering Committee for this purpose. Examples of possible Cooperative Resources include genomic/proteomic, imaging, or sophisticated flow cytometry facilities. The Steering Committee will determine procedures for the use of such Cooperative Resources, and will determine the scope of work and level of support based on CCHI priorities and requirements. Scientific Cores funded within individual Centers may be expanded to become Cooperative Resources using these Discretionary Funds available to the CCHI Steering Committee. Cooperative Resources may be housed at particular Centers or may be supported through subcontracts to other facilities. The Discretionary Funds will be managed by one of the awardee institutions selected by NIAID after award.

2.A.4. Arbitration Process

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Special Reporting Requirements

The annual progress report for the U19 award will use the standard PHS 2590 form. In addition, an executive summary and a detailed description of the work done to achieve the specific Milestones for that funding year shall be included. If Milestones have not been met, an explanation of what has been accomplished and the alternatives, solutions, and/or problems that exist must be provided. If the future Milestones need to be modified, updated Milestones and associated timelines must be included in the report and reviewed with the Program Officer. The Program Officer, in conjunction with the Steering Committee, will determine if major changes are appropriate and provide approval.

In addition to ongoing monitoring by Program staff, the NIAID plans to conduct a prospective and comprehensive evaluation of the Institute’s research portfolio in human immunology, which includes (but is not limited to) Centers funded under this announcement. The goal of this evaluation will be to assess the effectiveness of the CCHI program in helping to meet the research objectives of the NIAID mission, including the administrative oversight and managerial processes involved. Accordingly, areas of interest for the evaluation will include increasing the productivity of human immunology research; enhancing research capacity; and translating research results into improved prevention and treatment. To support this effort, the NIAID may request that the PD/PI(s) of each CCHI award participate in the design and conduct of the evaluation. In addition, the awardees may be contacted during or after the completion of this award for information helpful in assessing the overall impact of the program.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Helen Quill, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3013, MSC-6601
6610 Rockledge Drive
Bethesda, MD 20892-6601 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-435-4416
FAX: 301-480-2381
Email: hquill@niaid.nih.gov

2. Peer Review Contacts:

Priti Mehrotra, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 3138, MSC-7616
6700B Rockledge Drive
Bethesda, MD 20892-7616 (U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-435-9369; 301-496-2550
FAX: 301-480-2310
Email: pm158b@nih.gov

3. Financial or Grants Management Contacts:

Christy Leake
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2242, MSC-7614
6700B Rockledge Drive
Bethesda, MD 20892-7614(U.S. Postal Service or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: 301-402-5937
FAX: 301-493-0597
Email: cleake@niaid.nih.gov

Section VIII. Other Information

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Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

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

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

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

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

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

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

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

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

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

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

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

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

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