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), (http://www.niaid.nih.gov/)

Title: Hepatitis C Cooperative Research Centers (U19)

Announcement Type

Update: The following update relating to this announcement has been issued:
October 08, 2014 - This RFA has been reissued as RFA-AI-14-045.

This Funding Opportunity Announcement (FOA) is a reissue of RFA-AI-04-028.

Request for Applications (RFA) Number: RFA-AI-09-025

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

Key Dates
Release Date: April 7, 2009
Letters of Intent Receipt Date: July 6, 2009
Application Receipt Date: August 6, 2009
Peer Review Date: December, 2009
Council Review Date: January, 2010
Earliest Anticipated Start Date: April, 2010
Additional Information To Be Available Date (Url Activation Date): http://www.niaid.nih.gov/ncn/qa/revniaid.htm
Expiration Date: August 7, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Allergy and Infectious Diseases (NIAID) invites applications for Hepatitis C Cooperative Research Centers (HepC CRCs). These Centers will advance the understanding of hepatitis C virus (HCV)-host interactions, specifically the host immune response to infection, and the factors that tilt the balance between spontaneous or therapy-induced clearance and chronic persistence of HCV. Experimental observations will be validated and clinical relevance demonstrated, in appropriate, well-defined, patient cohorts. The underlying mission of the Centers is to close the gaps that currently exist with regard to defining successful immune response and identifying new targets for antiviral drugs, vaccines, and other therapeutic strategies for the prevention or treatment of acute and chronic HCV infection.
• Mechanism of Support. This Funding Opportunity Announcement (FOA) will utilize the NIH multi-project (U19) cooperative agreement grant mechanism.
• Funds Available and Anticipated Number of Awards. The NIAID expect(s) to award $4 million in total costs in response to this FOA, in FY 2010, to fund 4-5 new and/or renewal grants.
• Budget and Project Period. The budget for each HepC CRC is expected to range from $300,000 - $500,000 in direct costs per year. The total project period for an application submitted in response to this FOA may not exceed 5 years.
• 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/ 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.
• Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are permitted in response to this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936.

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(s) of Support
2. Funds Available

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

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

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 National Institute of Allergy and Infectious Diseases (NIAID) invites applications to participate in a cooperative research program to advance understanding of hepatitis C virus (HCV)-host interactions, specifically the host immune response to infection, and the factors that tilt the balance between spontaneous or therapy-induced clearance and chronic persistence of HCV. Each Hepatitis C Cooperative Research Center (HepC CRC) will be required to use appropriate, well-defined patient populations to validate experimental observations and to demonstrate clinical relevance. The overall goal of the HepC CRCs program is to increase knowledge of successful immune response to HCV infection that will lead to the identification of new targets for antiviral drugs, vaccines, and other therapeutic strategies for the prevention or treatment of acute and chronic HCV infection.

Background

Chronic infection with HCV is the cause of severe and often fatal progressive liver disease, including liver cirrhosis and primary liver cancer. No vaccines are available for the prevention of HCV infection, and between 70-80% of acute infections eventually become chronic. On average, approximately 50% of those treated for chronic infection cannot be cured. With an estimated 170 million chronic carriers of HCV worldwide, including 1.7 million in the US, the social, medical and economic burden of HCV infection is enormous.

The current standard-of-care treatment for HCV - a combination of pegylated interferon-? and the nucleoside analogue drug, ribavirin - has variable efficacy against different genotypes of HCV. The most urgent questions, still largely unanswered, pertain to how HCV persists despite the induction of generally robust interferon responses, ostensibly neutralizing antibodies, and measurable activation of T-cell function.

Recent progress has led to a better understanding of HCV infection, entry, and replication - largely through the landmark development of replicons, cell culture infection models for certain HCV genotypes, HCV chimeras and pseudotype viruses. For example, it is now known that 1) HCV proteins can inhibit key effectors of the interferon signaling pathways; 2) immune pressure drives the emergence of HCV escape mutants from T cells and antibodies; and, 3) T cell functions, e.g., proliferation capacity and durability of response, may be compromised in chronic infection. Various cytokines, suppressors and their cognate receptors have been implicated as influencing HCV clearance or persistence. Yet, mostly, these may only still be regarded as markers and their functional significance remains to be established. In most cases, the observations are essentially descriptive and mechanistic insights are lacking.

On the other hand, 20-30% of acute infections are spontaneously cleared and approximately 50% of chronic infections can be cured through treatment. And, even when initial therapy has failed, re-treatment or prolonged treatment has, on rare occasions, been successful. This suggests that even severely compromised immune systems can sometimes be restored by therapy, and that rational immune-based strategies may improve response rates. The exploration of radically new ideas may provide impetus to this effort. In addition to encouraging mechanistic studies on promising current ideas, this FOA invites applicants to propound and test well-reasoned fresh concepts and hypotheses even if such ideas depart from currently held views.

Objectives and Scope

This FOA supports studies to reveal the mechanisms through which a) acute HCV infection is spontaneously cleared, and b) chronic HCV infection may be cured by therapy. These studies should be more than observational, and should investigate mechanisms in detail. The clinical relevance of findings must be investigated in the appropriate HCV- infected human populations. Studies should be designed to add substantial new insights to current concepts.

Applicants should focus on the following objectives and other closely relevant questions:

1. Identify effectors of HCV-induced innate immune signaling; describe their mechanisms in HCV control; explain how HCV inhibits innate immune pathways.

2. Determine the mechanisms of the adaptive immunity in clearance of HCV infection and their functional collapse leading to virus persistence.

3. Clarify how the innate and adaptive immune responses are integrated to effect clearance of HCV infection.

4. Establish the role of antibodies in the control of HCV infection.

Clinical Studies

The clinical relevance of laboratory-derived observations can only be determined through clinical studies using well-defined cohorts of HCV-infected patients with different outcomes and prognosis. Therefore, applications must contain well integrated and scientifically related clinical studies. Studies may make use of samples obtained from human subjects in clinical trials funded through NIH or other sources.

Population cohorts may include intravenous drug users (IDU), African Americans, American natives, Hispanics, Alaskan natives, Hawaiian natives, and foreign populations with high prevalence or susceptibility to chronic HCV infection and liver disease, those with poor response to interferon therapy, and patients co-infected with HIV.

Potential applicants are strongly encouraged to contact the Program staff listed in Section VII. Agency Contacts, of this FOA to discuss the responsiveness of their proposed research.

This FOA will NOT support:

• Applications which focus on basic molecular studies on HCV replication or HCV protein expression, or their regulation.
• Applications involving the use of genomic or proteomic technologies, except as part of a very narrowly focused immune response discovery plan that includes mechanistic studies.
• Clinical trials.
• The development of new animal models.

HepC CRC Components

A HepC CRC (hereafter Center) must consist of at least two independent, but well integrated, scored research projects each employing unique and innovative approaches to address related questions. All Centers must include clinical studies using well-defined cohorts of HCV-infected patients. Studies may include the use of relevant and established animal models. The Center must be located within an institution in the US and headed by a Director, who is also the Principal Investigator and one of the Project Leaders. Each additional project must have a Project Leader, either at the Center home site or at another US or foreign institution. The Center Director will have responsibility for providing programmatic direction, coordination, and administrative management of the Center.

Scientific Core: A Scientific core facility may be proposed if common facilities or resources are to be used by at least two research projects in a Center. Resources may include specialized reagents, technology, patient cohorts or clinical cores, and databases. Scientific cores should be well-justified, and should not include facilities otherwise already available to the investigators. Scientific cores should address how resources, including clinical samples, may be made available to other Centers and investigators in the wider research community, as required by NIH policy. A detailed budget must be provided for each Core. The apportionment of dollars or percentage of dollars that will be required to support each research project should also be presented.

Administrative Core: An Administrative Core is required for the management of each Center. Applications should include details of organization, decision-making processes, regular evaluation of research within the Center, and data sharing. An Administrative Core budget may be requested for support staff, publication costs, telecommunications, and travel to mandatory annual Center meetings described below.

Annual HepC CRC Meetings

The NIAID will work with the Center Directors to organize a 1-2 day meeting each year, as needed, for key personnel of each Center to share recent findings and encourage collaborations. Funds for travel and accommodations should be included in the budget request for the Administrative Core for Center Directors. Travel costs for Project Leaders and Core Leaders may be included in the Administrative Core or individual projects or cores. All annual Center meetings will be held in the Bethesda, Maryland area or another NIAID-approved site. The initial meeting will be held within 2 months of award, if deemed necessary by the Project Officer.

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 NIH multi-project Cooperative Agreement (U19) grant award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use 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 under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

NIAID has not yet determined whether this FOA will be renewed beyond the duration of the present FOA.

2. Funds Available

• The NIAID expects to award $4 million in total costs, through this announcement in fiscal year 2010.
• 4-5 awards are expected to be made.
• The direct cost amount for individual awards is expected to range from $300,000 - $500,000 per year. The project period may not exceed 5 years.

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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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

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
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations

Foreign institutions are not eligible to apply as the primary applicant. However, applications may include foreign research components or collaborative sites.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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.

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

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.

Resubmissions. Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewals. Renewal applications will be permitted in response to this FOA.

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 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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

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 address 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 describe 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 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.

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.

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 of the multi-project application, followed by the Project and Core Leaders of the component research projects and cores, other key personnel, and then other significant contributors.

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 research project and core. A page reference should be included for the budget for each project and each core. Further, each research 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

Complete the Total Direct Cost line entries for all requested budget periods (years) and the Total Direct Cost for Entire Period of Support entry. Detailed budgets are required within the descriptions of each project and core (see below).

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 first, followed by those of other key personnel in alphabetical order.

7. Resources Format Page

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

8. 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 for new applications, and 30 pages for renewal applications. The multi-project application should be viewed as a confederation of interrelated research projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. 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, this section should also highlight past performance and the major accomplishments from the prior funding period. In addition to discussing results from individual projects, describe the synergy and collaborations that occurred. For individual research projects that will be continued, additional details should be provided in the Progress Report section of the Research Plan within the application for the Research Project.

9. Checklist

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

10. Appendix Materials

Refer to Section IV.6. Other Submission Requirements and Information, for instructions on submitting appendix materials.

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

B. Specific Instructions for Individual Research 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 research project.

Each individual Research Project must include:

• Cover page (see special instructions, below)
• Description & Key personnel (PHS 398 Form Page 2)
• Table of Contents (PHS 398 Form Page 3)
• Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications
• Resources Format Page
• Items 2-5 of the Research Plan as defined in the PHS 398 instructions
• Items 6-17 of the Research Plan, as appropriate

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 research project. This Cover Page will demarcate each individual research 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. Preclinical Evaluation of HIV Microbicides)

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

Human Subjects: (Yes or No)

If Yes, exemption number:

(or)

Institutional Review Board (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: $700,000

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 research 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 research project using Form Page 3 of the PHS 398.

4. Budget Pages (PHS 398 Form Pages 4 and 5)

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

5. 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).

6. Resources Format Page

Provide information on resources available for the project.

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

Item 2 -- Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the project's relationship to the multi-project program goals and how it relates to other projects or cores. This section is typically one page.

Item 3 -- Background and Significance: Use this section to describe how the proposed research will contribute to meeting the program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application.

8. Appendix

All appendix material should be collated as one body of material and submitted on CD.

C. 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.

Each Core must include:

• Cover page (see special instructions, below)
• Description & Key personnel (PHS 398 Form Page 2)
• Table of Contents (PHS 398 Form Page 3)
• Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications
• Resources Format Page
• Items 2-5 of the Research Plan as defined in the PHS 398 instructions
• Items 6-17 of the Research Plan, as appropriate

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. Budget Pages (PHS 398 Form Pages 4 and 5)

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

5. 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).

6. Resources Format Page

Provide information on resources available for the core.

7. Core Research Plan (Items 2-5 cannot exceed 10 pages for the Administrative Core and 15 pages for each Scientific Core,)

8. Appendix

All appendix materials should be collated as one body of material and submitted on CD.

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: July 6, 2009
Application Receipt Date: August 6, 2009
Peer Review Date: December, 2009
Council Review Date: January, 2010
Earliest Anticipated Start Date: April, 2010

3.A.1. Letter of Intent

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

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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

The letter of intent is to be sent by the date listed in Section IV.3.A.

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
6700-B 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 forms 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
6700-B 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 described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or 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 Principal Investigator 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 NIH Grants Policy Statement.

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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 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 and Information

All applications must include clinical studies using well-defined cohorts of HCV-infected patients, and must present the concept of the proposed research to include the hypothesis, study objectives, target population(s), and potential clinical sites. The application should provide sufficient detail to allow the reviewers to judge the scientific and technical merit. Samples may be derived from clinical studies or clinical trials that are planned, ongoing or completed and sponsored by any source of support. Each application must include a minimum of two interrelated research projects organized around a central scientific theme, as well as an Administrative Core. As noted previously, clinical trials will not be supported under this FOA.

The budget requested should include funds for the Center Director and Project Leaders to attend annual meetings at the NIH in Bethesda, Maryland or at another site as determined by NIAID staff.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Plan Page Limitations

See Section IV.2. Content and Form of Application Submission for Research Plan page limitations for the individual Hep C CRC components.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the 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 the 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 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 (e.g., 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 (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

It is anticipated that clinical specimens (e.g., blood samples, sera, biopsy material, etc.,) will be collected. Such material should be carefully archived and stored. NIH expects that, whenever possible, specimens would be made available to the research community upon request, following suitable review of the request and compliance with informed consent.

Section V. Application Review Information

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1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIAID and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

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

The following will be considered in making funding decisions:

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

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Review Criteria for Individual Research Projects

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

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

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

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

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application propound and test well-reasoned fresh concepts and hypotheses? Are the studies designed to add substantial new insights into existing knowledge?

Approach. Are the overall strategy, methodology, and analysis well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Review Criteria for Cores

Administrative Core

• Is the administrative and organizational structure appropriate and adequate to the attainment of the objective(s) of the proposed program?
• Is the management plan for fiscal accountability and communication within the Center appropriate?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the program appropriate?
• Are the experience, level of commitment, and availability of the Administrative Core Leader and administrative staff adequate to manage the program?

Scientific Cores (if applicable)

• Is provision of resources and core services for the individual Research Projects critical and justified?
• Is the relationship of a scientific core to the central focus of the overall program strong?
• Is the quality of the relevant facilities or services provided and criteria for prioritization and usage appropriate?
• Are the qualifications, competence, and commitment of the Core Leader and key personnel appropriate?

Review Criteria for Evaluating the Overall Application

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

• Is the program as a whole scientifically compelling? Is there coordination and synergy of the individual research projects and cores towards the achievement of the central objectives of the Center?
• Are the overall program goals significant and focused on studies that meet the objectives of the FOA?
• Will the integration of the individual projects into a single program be more beneficial than pursuing each project independently?
• Does the Center Director have the leadership and scientific ability to develop an integrated and focused research program?
• Will the Center Director and other Project/Core Leaders devote adequate time and effort to the program?
• For renewal applications, what are the accomplishments and progress achieved during the prior funding period?
• Is there adequate evidence of sufficient institutional support for the Center Director in terms of laboratory space, equipment and other resources?

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

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

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

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

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

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

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

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html ); and 3) 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 or 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.

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 on item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The Center Director has overall responsibility for the Center and its components. This includes the general direction and objectives of the research, as well as ensuring conformity with the guidelines of the FOA. The Center Director will coordinate the activities of the individual projects - which are primarily the responsibility of the Project and Core Leaders to conduct, as described in the Research Objectives section. Publications and presentations at conferences of studies supported under this initiative must specifically acknowledge this NIAID support. NIAID may specifically request the Center Director and Project Leaders for information on projects for the purpose of internal reports and review pertaining to this cooperative agreement.

The Center Director agrees to accept close coordination of the project as stated below under NIH Responsibilities.

Intellectual Property

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

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

The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, and reports to the NIAID, or other mechanisms.

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

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.

The NIAID/NIH Project Scientist will support the Center's activities by working closely with the Center Director and project leaders to be appraised of ongoing progress, coordinate research among Centers so as to facilitate collaborations, and assist with access to other NIH resources available to the Program. The NIAID Project Scientist will convene annual meetings as needed, of the Center Directors and senior investigators of all the Centers in order to discuss progress, identify new directions and collaborations, and promote sharing of resources.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

The Cooperative Agreement implies a close relationship between the Center and the NIAID, which requires cooperation and participation of NIAID staff in scientific discussions and Center collaborations. The potential for such collaboration is enhanced by the network organization of the Centers, and Center investigators are expected to take advantage of this unique resource.

2.A.4. Arbitration Process

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

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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 (program), peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Rajen Koshy, Ph.D
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Disease
Room 4009, MSC-6604
6610 Rockledge Drive, Room 4009
Bethesda, MD 20892-4009
Telephone: (301) 402-8550
Fax: (301) 402-1456
Email: rkoshy@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
6700-B 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:

Julia Torres
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2247, MSC-7614
6700-B Rockledge Drive
Bethesda, MD 20892-7614
Telephone: (301) 451-2690
Fax: 301-493-0597
Email: torresju@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 (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This 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. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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