Part I Overview Information

Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www2.niddk.nih.gov/ )

Title: Beta Cell Biology Consortium (U01)

Announcement Type
This is a reissue of RFA-DK-04-018.

Request For Applications (RFA) Number: RFA-DK-09-011

Catalog of Federal Domestic Assistance Number(s)
93.847

Key Dates
Release Date: August 14, 2009
Letters of Intent Receipt Date: October 26, 2009
Application Receipt Date: November 23, 2009
Peer Review Date(s): February/March, 2010  
Council Review Date: May 2010
Earliest Anticipated Start Date: July 2010
Expiration Date: November 24, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The National Institute of Diabetes and Digestive and Kidney Diseases invite new U01 applications to participate in a consortium of investigators, the Beta Cell Biology Consortium (BCBC); www.betacell.org . The BCBC will work collaboratively to facilitate research in the following areas: 1) use cues from pancreatic development to directly differentiate pancreatic beta cells and islets from stem/progenitor cells for use in cell-replacement therapies for diabetes; 2) determine how to stimulate beta cell regeneration in the adult pancreas as a basis for improving beta cell mass in diabetic patients; 3) determine how to reprogram progenitor/adult cells into pancreatic beta-cells both in-vitro and in-vivo as a mean for developing cell-replacement therapies for diabetes; and 4) investigate the progression of human type-1 diabetes using patient-derived cells and tissues transplanted in humanized mouse models.  The BCBC will be responsible for collaboratively generating the necessary reagents, mouse strains, antibodies, assays, protocols, technologies and validation assays that are beyond the scope of any single research effort proposed by the investigators.
• Mechanism of Support. This FOA will utilize the U01 grant mechanism.
• Funds Available and Anticipated Number of Awards. The total amount of funding that the NIDDK expects to award through this announcement in FY2010 is $12 million. The anticipated number of awards is 6-10. Although the financial plans of the NIDDK provide support for the first two years of this program, awards pursuant to this FOA, particularly in years 3 to 5 of the awards, are contingent upon the availability of funds.
• Budget and Project Period.  The total project period for an application submitted in response to this funding opportunity may not exceed five years. Expected direct cost amount for individual awards is $400,000 to $1,500,000.
• 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 PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• 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
• 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

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

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

Section I. Funding Opportunity Description

1. Research Objectives

Background

Type 1 and type 2 diabetes (T1D and T2D) result from the anatomical or functional loss of insulin-producing beta cells of the pancreas.  Replacement of these cells through transplantation and/or regeneration could offer lifelong treatment for diabetes.  Major obstacles in implementing treatment include the lack of sufficient islet cell tissue for transplantation, the absence of a means to increase residual beta cell mass, and the inability to prevent the immune system from destroying of newly introduced/generated beta cells in the diabetic environment found in the recipient patient.  The generation of an alternative source of pancreatic islet cells derived from human stem/progenitor cells or from reprogrammed progenitor/adult cells could provide a limitless source of islet cells for cell replacement therapies. Alternatively, the identification of molecules that can stimulate beta cell regeneration could lead to the replenishment of beta cell mass without the need for transplantation. Finally, the development of better animal models of the human T1D using patient-derived tissues could lead to a better understanding of disease progression, strategies to protect engrafted or regenerated beta cells from autoimmune destruction, and preclinical platforms to test the efficacy of novel cell-replacement protocols.

The BCBC is a science consortium of cooperative agreements that originated in 2001 through an RFA-DK-01-014 http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-01-014.html . The consortium was created by the NIDDK as a direct response to recommendations of the Congressionally-established Diabetes Research Working Group that developed a strategic plan for research in diabetes and called for an increase in basic research on the control and regulation of islet cell differentiation, growth and development. Accordingly, the BCBC has brought a team-based approach to the generation of new research tools, reagents, and technologies vital for developing new cellular therapies in diabetes. In view of the consortium’s success at accelerating discoveries and generating research resources in the areas of beta cell development, generation of beta cells from stem cells and beta cell regeneration, the NIDDK has decided to support a new version of this collaborative effort through funding of new, outstanding projects in specific scientific areas described below.

In addition to investigator-initiated research projects, the BCBC supports an administrative infrastructure located at Vanderbilt University that oversees collaborative research cores designed to coordinate efforts in creating key research tools that will support studies relevant to the BCBC mission. The BCBC will be comprised of awardees from RFA-DK-09-011, as well as the existing BCBC Coordinating Center (BCBC CC) located at Vanderbilt University.

Research Objectives

This FOA is intended to provide support for new U01 projects for the BCBC in order to achieve the following research goals: identify signaling factors, including secreted peptides and small molecules, that regulate the final steps of pancreatic development as a strategy for producing efficiently large numbers of highly functioning beta cells from stem/progenitor cells; discover factors that can stimulate islet cell growth and regeneration; develop cell reprogramming strategies to generate beta cells from progenitor or adult cells; create models of the human T1D using patient-derived tissues and humanized mouse models to study human beta cells/islets in the context of a human autoimmune environment. 

Diverse disciplines such as developmental biology, stem cell biology, cell reprogramming, epigenetic regulation, regenerative medicine, endocrinology, mouse genetics, immunology and transplantation surgery will be needed to achieve the BCBC’s scientific objectives. In addition, a multifaceted, interdisciplinary, coordinated and collaborative approach on several fronts will be required to generate the key reagents, assays and strategies required for the development of novel cellular therapies in diabetes.  Therefore, 1) a strong emphasis on team science should be reflected in the proposals written in response to this announcement, and multi-PI applications are strongly encouraged and 2) at least 50% of the application should be directly related to the generation of novel resources and approaches, which could include development of new reagents, assays, protocols, or animal models, and/or application of a new technology.

While the use of animal models of pancreatic development and beta cell regeneration is still the most efficient way to identify new signals and pathways regulating the formation of mature beta cells, findings in these areas may be of little relevance to human development and/or biology, and to the long-term translational goals of the consortium. Therefore, applicants using animal models/cells as a primary research tool should clearly articulate strategies whereby the relevance of the observations/discoveries made in animal models will be validated using human cells or tissues. These validation steps can either be an integral part of the original grant proposal, or be developed later through collaborations initiated during the funding period using the subcontract mechanisms managed by the BCBC CC.

The research objectives proposed by the applicant should be focused on at least one of the four targeted scientific goals described below:  1) use cues from pancreatic development to directly differentiate beta cells from human stem/progenitor cells, 2) enhance functional beta cell mass, 3) reprogram progenitor or adult cells to beta cells, and 4) use patient-derived tissues and humanized mouse models to generate and study human beta cells/islets in the context of a human autoimmune environment.

Discover late developmental pro-beta cell signals and efficiently produce of human beta cells:

A goal of this FOA and the BCBC is to discover signals (developmental, epigenetic, chemical) that can lead to the production of a fully functioning pancreatic beta cell. Tremendous progress has been achieved in programming mouse and human embryonic stem cells (ESCs) to a stage mimicking that of multipotent pancreatic progenitor cells (e.g. Pdx1- and Ptf1a-positive cells). However, the specific signals that induce the formation of late pancreatic progenitors (e.g. Ngn3-positive cells), or the partitioning of such late progenitors into the different pancreatic islet types, remain largely unknown. A focus of the consortium in the next five years should be the discovery of pro-beta cell signals that function beyond the Pdx1 induction step, as well as the description of the epigenetic controls that could allow one to prospectively program stem cells into functional beta cells. Areas of emphasis may include but are not restricted to:

1.     Identify secreted factors, small molecules, extracellular matrices, genes, epigenetic regulators and/or protein transduction strategies that could allow the prospective programming of human ESC- or induced human pluripotent stem cell (iPSC)-derived Pdx1-positive progenitors to mature beta cells in-vitro.

2.     Assess the chromatin/epigenomic state of mature beta cells and their progenitors, and use this knowledge to devise differentiation strategies and help determine a mature “beta cell” signature.

3.     Develop techniques that would allow for the isolation, purification and the scale-up in producing defined progenitor populations and their endocrine pancreas progeny.

Enhancement of beta cell mass:

A goal of this FOA and the BCBC is to understand the mechanisms of beta cell regeneration in the adult animal as well as in human islet. Areas of emphasis may include but are not restricted to:

1.     Better understand the cell types, signaling pathways and genes that control islet cell mass and beta cell replication/regeneration, that are relevant to the regenerative capacity of the human islet.

2.     Identify small molecules and secreted factors that promote expansion of human beta cell mass

3.     Determine the regenerative capacity of human islets in a variety of pathophysiological settings (hyperglycemia, inflammation, etc,) following transplantation in immunodeficient mouse models.

4.     Identify immunosuppressive drugs that do not inhibit beta cell regeneration and test the effects of drugs often used by diabetic patients for their compatibility with beta cell regeneration and beta cell proliferation/survival

5.     Develop new strategies to assess beta cell mass in-vivo.

Transdifferentiation or reprogramming of progenitor or adult cells to beta cells:

Recent evidence has demonstrated that it is possible to directly reprogram a fully committed, differentiated cell, from one lineage into another, thereby bypassing steps of either de-differentiation or reversion to a pluripotent state.  A goal of this FOA and the BCBC is to find strategies to generate large quantities of fully functional beta cells through the transdifferentiation or direct reprogramming of other progenitor or adult cell types in-vitro and/or in-vivo. Areas of emphasis may include but are not restricted to:

1.     Understand the mechanisms (epigenetic, developmental, etc…) of how the process of transdifferentiation or reprogramming to beta cell takes place

2.     Identify and use small molecules rather than viral reprogramming inducers to achieve reprogramming and the safe generation of beta cells for replacement therapies

3.     Generate human pancreatic beta cells beginning with other cell types that could readily be obtained from patients with T1D

4.     Explore strategies for the in vivo reprogramming of non-beta cells into regulated insulin-producing cells

Reconstructing human T1D in a mouse using patient-derived iPSCs:

Patient-derived iPSCs have the potential to help us understand the pathogenesis of diseases resulting from complex genetic predispositions such as T1D, become an expandable and personalized source of transplantable cells, and test future T1D treatments.  Thus, the BCBC will consider projects leading to the generation and use of T1D patient-derived iPSCs. Areas of emphasis may include but are not restricted to:

1.     Derive clinical-grade iPSCs from T1D patients using small molecules rather than viral reprogramming inducers

2.     Recapitulate both normal and pathologic human tissue formation in vitro

3.     Develop humanized mouse pancreata from non-diabetic subjects and T1D patients

4.     Use human iPSC technology to create murine models of T1D that would include the generation of functional beta cells as one of the key components

5.     Use T1D patient-derived iPSCs to test whether a patient’s own immune system will target his/her islet-like cells generated in vitro.

6.     Engineer T1D patient-derived iPSCs in order to produce beta-cells that are protected from autoimmune destruction following transplantation

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

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the U01 award mechanism(s).
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 Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

The NIDDK intends to commit approximately $12 million in total costs in FY 2010 to fund 6-10 grants in response to this announcement. An applicant may request a project period of up to 5 years and a budget for direct costs of up to $1.5 million per year.  Although the financial plans of the NIDDK provide support for the first two years of this program, awards pursuant to this FOA, particularly in years 3 to 5 of the awards, are contingent upon the availability of funds. 

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

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
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. 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 required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

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 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.  

Section IV. Application and Submission Information

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.

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.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs 

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

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: October 26, 2009
Application Receipt Date: November 23, 2009
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 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:

Francisco Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892
Telephone: (301) 594-8897
FAX: (301) 480-4126
Email: fc15y@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:

Francisco Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892
Telephone: (301) 594-8897
FAX: (301) 480-4126
Email: fc15y@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 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 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

The BCBC will be comprised of awardees under this FOA in addition to the BCBC Coordinating Center (BCBC CC).  The BCBC CC will undergo renewal in a separate solicitation.  To promote the development of a collaborative program among the award recipients, the Principal Investigator is expected to attend BCBC Steering Committee meetings twice a year. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents. At the meetings, participants will discuss bioinformatics, coordination, sharing, and a means of informing the community about progress made by the Consortium. Funds should be requested to attend Steering Committee meetings as well as other collaborative meetings of the BCBC.

During the course of the funding period, technologies will improve and the rate of progress and scope of the research may change. It is expected that the Principal Investigators, in consultation with NIDDK program staff, will make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, to maintain excellent coordination with the other projects funded under this FOA, and to incorporate new technological advances.

The “Research Plan” should have a section entitled “Collaboration within the BCBC”. In this section”, the applicant should describe how he/she believes his/her unique expertise can contribute to the collective effort of the BCBC. The applicant should also provide evidence of their intention to work together with other members of the BCBC to share ideas, develop future collaborations, and generate common tools and reagents.

The BCBC is a collaborative effort that requires frequent interactions of awardees among themselves and with the NIH. Applicants must explicitly indicate their willingness to: participate in Steering Committee Meetings (2 times per year), regular telephone conference calls; cooperate with other awardees in the development and design of research priorities, especially regarding resources, and must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Research Plan Page Limitations:

Sections 2-5 of the Research Plan Attachments of the PHS 398 Research Plan component may not exceed 25 pages, including all tables, graphs, figures, diagrams, and charts.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

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/.

In generating unique research tools, applicants should describe their willingness to cooperate and coordinate with the research activities and priorities of the BCBC. All protocols, antibodies, vectors, cells, animals and data generated through the BCBC will be made freely available to the general scientific community. In working with the BCBC CC, the BCBC Executive Committee and the BCBC Steering Committee, applicants must agree to distribute unique resources developed through the BCBC in a timely manner.

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

1. Criteria

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

2. Review and Selection Process

Upon receipt, applications will be reviewed for completeness by the CSR. NIDDK will conduct the review. The Chief of the Review Branch, assigned SRA, and NIDDK Program Staff will conduct an administrative review to determine if the application is responsive to the FOA, or missing any information. Incomplete applications will not be reviewed and will be returned to the applicant.

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 National Institute of Diabetes and Digestive and Kidney Diseases 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 an impact/priority score.
• Receive a written critique.
• Receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory 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 .
• Programmatic balance and representation in the final set of funded grants of the four key research areas described in Part II, Section I.1. “Research Objectives”.

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. 

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 major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

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

Investigator(s).  Are the PD/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? Have the investigators demonstrated their ability to work collaboratively in the past?

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

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

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

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/priority 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).

Applications from Foreign Organizations.  Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

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 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.

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 Principal Investigator is a member of the Beta Cell Biology Consortium (BCBC) and will have the primary responsibility for:

• Defining objectives and approaches, and planning, conducting, analyzing, and publishing results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award;
• Conducting the research supported by the project in accordance with the terms and conditions of the award;
• Participating, when being asked, as a rotating and voting member of the Executive Committee as described below;
• Participating as a permanent, voting member(s) of the steering Committee as described below;
• Contributing to and implementing the goals, priorities, procedures, and policies agreed upon by the Steering Committee;
• Coordinating and cooperating with the other components of the BCBC and with the NIDDK staff;
• Contributing to BCBC Core resources and serving on BCBC subcommittees or on the BCBC Executive Committee as needed;
• Sharing both data and unique research resources that are generated by the projects in concordance with the BCBC policies.

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 NIDDK Program Director identified in the Notice of Grant Award will be responsible for the normal stewardship and monitoring of the award and will serve as the NIDDK Project Scientist.

The NIDDK Project Scientist will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice and coordination.  The dominant role and primary responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NIDDK Project Scientist.

The NIDDK Project Scientist will have substantial involvement in the project above and beyond normal stewardship and monitoring of the award, as described below:

• Being a voting member of the Executive Committee
• Being a voting member of the Steering Committee and, as determined by that
  committee, its subcommittees;
• Being the contact point for all facets of the scientific interaction with awardee(s).  As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific issues; 
• Serving as a resource with respect to other ongoing NIDDK activities that may be relevant to the research of the BCBC in order to facilitate compatibility and avoid unnecessary duplication of effort.

Responsibilities as NIDDK Program Director:

• Retaining overall programmatic responsibility for the award, and will clearly specify to the awardee the name(s) and role(s) of any additional individuals with substantial involvement in the project and the lines of reporting authority;
• Interacting with the Principal Investigator (s) on a regular basis to monitor research progress.  Monitoring may include:  regular communications with the Principal Investigator and staff, periodic conference calls for discussions with awardee research teams, quality control, fiscal review, and other relevant matters; participation to Executive Committee teleconferences; attendance at Steering Committee meetings, External Advisory Board Meetings, and related meetings.  The NIDDK retains, as an option, periodic external review of progress;
• Reviewing and approving applications of the Collaborative Bridging Program, the Pilot and Feasibility Program and the Seeding Grant Program to insure that they are within the scope of peer review and NIH guidelines; 
• Making recommendations for continued funding based on: a) overall research progress, b) cooperation in carrying out the research (e.g. attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award, and c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
  

2.A.3. Collaborative Responsibilities (optional)

BCBC Executive Committee (EC)

• The Executive Committee of the BCBC will consist of five voting members: the Director of the BCBC CC, the NIDDK Project Scientist, the Associate Program Director, two other members of the NIDDK program staff, and two rotating members chosen among the principal investigators that compose the Steering Committee (SC).
  
• The rotating members will serve up to two-year terms and will be nominated on an annual basis by the EC, and confirmed by vote of the SC at the fall meeting.
  
• The EC will perform the secondary review of all NIH-funded P&F grant programs that are undertaken and make all final funding decisions. Award or declination letters will then be written by the Director of the CC, and then distributed by the CC.
  
• The EC will determine the leadership of all core facilities.
  
• The EC will periodically review the progress of core facilities, collaborative bridging grants, and make recommendations for improvement. Biannual reports will be prepared by each core facility to coincide with the two SC meetings.
  
• The EC will, if needed, discuss and evaluate new projects for existing cores, as well as new cores. Based on feedback from the SC, the EC will implement the creation of new core projects or cores.
  
• The EC will be responsible for organizing the yearly fall “BCBC Principal Investigator Retreat”, and for organizing a Committee that will be responsible for the planning of the spring “BCBC Scientific Retreat”. 
  
• The EC will have a standing monthly teleconference call that will be chaired by the Director of the BCBC CC. Any EC member may place items on the agenda. These should be communicated in advance of the meeting to the Program Coordinator who will distribute these to all members no later than one day in advance.

BCBC Steering Committee (SC)

• The Steering Committee has primary responsibility to establish priorities, develop common protocols, and review progress.  The Steering Committee will refine the BCBC scientific objectives consistent with progress in the BCBC components and other laboratories.  Major scientific decisions regarding BCBC core data and resources, as well as setting scientific priorities for special programs such as the Pilot and Feasibility Program will be determined by the Steering Committee.  The Steering Committee may be asked to document progress in written reports to the NIDDK Program Director, and will provide supplementary reports upon request. 
• The Steering Committee will be composed of the Principal Investigator from each U01 project, the Director of the Coordinating Center, and the NIDDK Project Scientist. Each member of the Steering Committee will have one Steering Committee vote.  The chairperson will be the Director of the Coordinating Center. In addition, the NIDDK Associate Program Director will also attend all of these meetings as a non-voting participant to provide additional information and to summarize actions that are taken.
• There will be two Steering Committee meetings annually, one in the Spring and the other in the Fall.
• The Steering Committee may, when necessary, invite additional, non-voting scientific advisors to the meetings at which research priorities and opportunities are discussed.  The NIDDK reserves the right to augment the scientific expertise of the BCBC when necessary.  
• At the Fall meeting each year, the Steering Committee will formulate plans for the Fall Investigator’s retreat or any symposia to be held.

The BCBC members may be asked to serve on subcommittees, scientifically review applications for special programs such as the Pilot and Feasibility Program, as it is deemed appropriate; the NIDDK Project Officer will serve on subcommittees as appropriate.  NIDDK staff with special expertise may serve on subcommittees at the request of the Steering Committee.  Subcommittee chairs will be selected from the Steering Committee and will report progress at Steering Committee Meetings and lead discussions at the Annual Investigator’s Retreat.

BCBC External Evaluation Committee:

An independent External Evaluation Committee has been established by the NIDDK. The External Evaluation Committee will review periodically interim progress of the U01s and BCBC CC and report to NIDDK staff. Members of the External Evaluation Committee may also be asked on an ad hoc basis to participate to the peer review of applications for new research initiatives such as the Collaborative Bridging Program, the Pilot and Feasibility Program and the Seeding Grant Program.

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 regulations 42 CFR Part 50, Subpart D and HHS regulations 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

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:

Olivier Blondel, Ph.D.
BCBC Program Director
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 796
Bethesda, MD 20892
Telephone: (301) 451-7334
FAX: (301) 480-0475
Email: blondelol@niddk.nih.gov

2. Peer Review Contacts:

Francisco Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892
Telephone: (301) 594-8897
FAX: (301) 480-4126
Email: fc15y@nih.gov

3. Financial or Grants Management Contacts:

Todd Le
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 726
Bethesda, MD 20892
Telephone: (301) 594-7794
FAX: (301) 594-9523
Email:tl139s@nih.gov

Section VIII. Other Information

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.