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 (NIH/NIDDK), (http://www.niddk.nih.gov)
National Heart, Lung and Blood Institute (NIH/NHLBI), (http://www.nhlbi.nih.gov)
National Institute of Neurological Disorders and Stroke (NIH/NINDS), (http://www.ninds.nih.gov)

Title: Animal Models of Diabetic Complications Consortium

Announcement Type
Renewal of RFA-DK-01-009.

Request For Applications (RFA) Number: RFA-DK-05-011

Catalog of Federal Domestic Assistance Number(s)
93.849, 93.837, 93.853

Key Dates
Release Date: August 17, 2005
Letters of Intent Receipt Date(s): October 21, 2005
Application Receipt Dates(s): November 18, 2005
Peer Review Date(s): February – March 2006
Council Review Date(s): May 31 – June 01, 2006
Earliest Anticipated Start Date: September 01, 2006
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: November 19, 2005

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

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
   4. Intergovernmental Review
   5. Funding Restrictions

 Section V. Application Review Information
   1. Criteria
   2. Review and Selection Process
     A. Additional Review Criteria
     B. Additional Review Considerations
     C. Sharing Research Data
     D. Sharing Research Resources
   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

Better animal models of human diabetic complications are needed to improve our understanding of disease pathogenesis and to permit testing of prevention, detection and therapeutic strategies. The intent of this RFA is to assemble a cross-disciplinary group of investigators to form Pathobiology (PB) Sites that will support the Animal Models of Diabetic Complications Consortium (AMDCC). The mission of the AMDCC is to develop innovative models that closely mimic the complications of human diabetes. The AMDCC focuses on mouse models to (1) provide a framework for the discovery of genes and cellular pathways that generate susceptibility or provide resistance, and (2) furnish targets for intervention and treatment.

Research Topics

In the next project period the AMDCC will consist of up to 14 cooperating Pathobiology (PB) Sites that are supported by a Mouse Generation and Husbandry Core (MGHC) and a Coordinating and Bioinformatics Unit (CBU). The MGHC will provide expertise and facilities needed to generate new mouse models of diabetic complications as directed by the AMDCC Executive Steering Committee. The CBU will provide administrative coordination and bioinformatics support. The AMDCC will also work closely with the Mouse Metabolic Phenotyping Centers (MMPCs) to ensure that all models are fully phenotyped. The MGHC, MMPCs and CBU will be awarded separately and are described briefly in Sections I.4-6 below.

Each AMDCC PB Site will have expertise and experimental focus in either diabetic complications OR biochemical pathways thought to be involved in the initiation, maintenance and/or severity of diabetic complications.

Diabetic complications to be examined include:

Biochemical pathways that might serve as a focus for an AMDCC PB Site include, but are not limited to:

Investigators are asked to submit an application (1) providing scientific rationale for generating up to two new mouse models that will faithfully replicate one or more diabetic complications, and (2) proposing hypothesis-driven specific aims for discovering and characterizing the basic pathophysiologic mechanisms underlying the complication being studied in the mouse model(s).

The AMDCC Executive Steering Committee will be responsible for the subsequent selection and prioritization of models proposed by PB Sites. The list of AMDCC-sponsored strains will be forwarded to the MGHC for production following concurrence by the AMDCC External Advisory Board (EAB) and NIH staff. As sufficient numbers of animals are generated, new models will be distributed back to the PB Sites for detailed investigation of pathophysiology and organ-specific phenotyping. New models will also be distributed by the MGHC to separately funded MMPCs for additional routine phenotyping, and will ultimately be made available to the greater scientific community (described in Section IV.6).

It is anticipated that the AMDCC PB Sites will support development of approximately 10-20 consortial strains. All phenotyping data (from the PB Sites, MGHC and MMPCs) will be sent to a central bioinformatics core housed in the AMDCC CBU.

Consortium Activities and Administrative Structure
The AMDCC will consist of up to 14 cooperating Pathobiology (PB) Sites, a Mouse Generation and Husbandry Core (MGHC) and a Coordinating and Bioinformatics Unit (CBU). Guidance and oversight will be provided by an Executive Steering Committee (ESC) and an External Advisory Board (EAB). The MGHC will provide expertise and facilities needed to generate 10-20 unique mouse models of diabetic complications as directed by the AMDCC ESC. The MGHC will be awarded separately. The CBU will provide administrative coordination and bioinformatics support for the Consortium. The AMDCC CBU will be shared with the MMPCs (http://www.mmpc.org) and will be competed through a separate RFA (http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-05-012.html). The activities of the MGHC, MMPCs and CBU are described briefly in Sections I.4-6 below.

Consortium Activities and Responsibilities
The Principal Investigator must agree to be an active participant in Consortium-wide activities as deemed necessary by appropriate oversight committees. Such activities may include development of Consortium publications describing model generation, validation criteria and phenotyping best practices; nomination of models for access to AMDCC cores and facilities; timely transfer of data to the AMDCC CBU; facilitating phenotypic analysis of AMDCC strains by the MMPCs.

Executive Steering Committee
The Principal Investigator must agree to participate in an Executive Steering Committee (ESC) that will meet monthly by teleconference and twice each year in person to encourage the exchange of information within the AMDCC. The ESC will consist of the PIs of Pathobiology Sites, Directors of the CBU and MGHC, NIH Project Scientists and Project Officials, and other AMDCC personnel as needed. The Chair will be chosen from among the Pathobiology Site PIs and may rotate on an annual basis. The role of the NIH Project Scientist is described under COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF THE AWARD, Section VI 2.A.2. The Project Official is responsible for reviewing annual progress of the AMDCC and signing-off on Grant Progress Reports. The purpose of the ESC will be to discuss and evaluate concerns and cooperative activities of the AMDCC at-large. The ESC may form and charge other subcommittees as needed.

A major goal of the ESC will be to identify and subsequently prioritize ideas for generating new mouse models to advance complications research. This prioritized list will be forwarded to the MGHC for production following concurrence by the EAB and NIH Staff. In addition, regular ESC meetings will provide a forum for sharing skills, ideas, technology, data, and biological reagents among participating AMDCC member sites. At the meetings, participants will also discuss quality assurance, bioinformatics, project coordination, protocol consistency, test comparisons across background strains and training. If voting is necessary for an action item, individual PIs and NIH staff hold one vote each. The Executive Steering Committee will discuss and evaluate subcommittee and consortial activities and provide feedback to subcommittee leaders at least bi-annually; implement changes in subcommittee membership or direction if needed; discuss and evaluate new projects and collaborative activities.

External Advisory Board
AMDCC PIs must indicate their intention to be responsive to recommendations provided by an independent External Advisory Board (EAB). Members of the EAB will be nominated by the Executive Steering Committee in collaboration with NIH Project Scientists, and will be invited by NIH personnel. APPLICANTS SHOULD NOT SUGGEST NAMES FOR ADVISORY BOARD MEMBERS IN THEIR APPLICATION. A chairman will be chosen from among the EAB membership, who will be accomplished senior scientists from academia and industry with backgrounds in diabetic complications, animal models, mouse genetics and technologies associated with mouse phenotyping. The EAB will meet annually in conjunction with one of the semi-annual meetings of the ESC to review interim progress of the AMDCC and will provide an annual report and recommendations to the NIH and to the ESC. If voting is necessary for an action item, members of the EAB and the EAB chair hold one vote each. The ESC will discuss implementation of EAB recommendations, plan a strategy and timeline for making these changes, and report back to the EAB in a timely fashion.

PI interactions with the MGHC and CBU
The AMDCC ESC will be asked to prioritize models for the Consortium that will be generated by the MGHC. A brief description of the MGHC, to be awarded separately, can be found in Section I.4 below. The AMDCC will support the production of approximately 10-20 consortial strains chosen and prioritized by the ESC. The choice and prioritization of models by the ESC will reflect both scientific appeal and best judgment to assure representation of complications across all relevant organs and body systems. ESC recommendations for model derivation, validation and characterization will be approved by the EAB and NIH Program staff. AMDCC PIs must state their willingness to provide data to the CBU in a timely fashion. Further description of the AMDCC CBU can be found in Section I.6 below.

Description of the AMDCC Mouse Generation and Husbandry Core (MGHC)
The AMDCC Mouse Generation and Husbandry Core will be awarded separately. Activities to be carried out by the MGHC under the direction of the AMDCC Executive Steering Committee include: (1) production of transgenic, knock-out or knock-in strains, (2) routine and specialized husbandry (e.g. diabetes induction protocols, specialized diets, etc.), (3) routine phenotyping (e.g. glycemia, insulinemia, glucosuria, blood pressure, etc.) , (4) transfer of strains to MMPCs for phenotyping under the direction of the AMDCC ESC and EAB, (5) transfer of strains to PIs at designated PB Sites, and (6) transfer of strains to an NIH-supported repository as directed by the AMDCC ESC and EAB.

Description of the Mouse Metabolic Phenotyping Centers (MMPCs)
The mission of the MMPCs is to advance biomedical research by providing the scientific community with standardized, high-quality metabolic and physiologic phenotyping services for mouse models of diabetes, diabetic complications, obesity and related disorders. Information about the current MMPCs, including a catalog of services, policies and guidelines, can be found at http://www.mmpc.org/.

The MMPCs are staffed by experts in state-of-the-art technologies and provide standardized procedures to characterize metabolism, body composition, energy balance, feeding behavior, activity, organ function, tissue pathology, and other physiologic, anatomic or pathological alterations that may occur in mice. The MMPCs will work closely with the AMDCC to provide reproducible and robust phenotyping for AMDCC-generated mouse strains as directed by the AMDCC ESC and EAB.

Methodologies proposed by the Pathobiology Sites should not overlap with MMPC services.

Description of the shared MMPC-AMDCC Coordinating and Bioinformatics Unit (CBU)
The AMDCC Coordinating and Bioinformatics Unit (CBU) will be shared with the Mouse Metabolic Phenotyping Centers (MMPCs; http://www.mmpc.org/) and will be competed through a separate RFA (http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-05-012.html). Activities to be undertaken by the CBU include: (1) provide clerical and administrative support, (2) maintain and manage the central database, (3) distribute funds and oversee financial management of Consortium related expenses, (4) update and maintain the AMDCC intranet and internet websites, and (5) promote the Consortium via advertising and through facilitating collaborative efforts.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the U01 award mechanism(s).

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/modular/modular.htm).

The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator 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". This initiative encourages applications for Pathobiology Sites to support years 6-10 of the AMDCC project. Plans to continue beyond year 10 will depend on success, opportunity and needs in the diabetes complications research community, and the availability of funds.

2. Funds Available

The participating Institutes intend to commit approximately $5.25 million dollars in FY 2006 to fund 14 new and/or competing continuation awards for AMDCC Pathobiology Sites in response to this RFA. Applicants may request a project period of 5 years and up to $250,000 direct costs per year. The earliest anticipated start date for awards made in response to this RFA is September 01, 2006.

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.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

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

2. Cost Sharing or Matching

Cost-sharing or matching is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

Investigators may submit more than one application for this RFA provided there is no budgetary or scientific overlap.

Applications proposing the generation of non-mouse models of diabetic complications will be considered non-responsive.

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) 435-0714, 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 Dun & Bradstreet (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 on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide a unique research opportunity not available in the U.S.

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

Letter of Intent Receipt Date: October 21, 2005
Application Receipt Date(s): November 18, 2005
Peer Review Date: February – March 2006
Council Review Date: May 31 – June 01, 2006
Earliest Anticipated Start Date: September 01, 2006

3.A.1. Letter of Intent

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

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

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

The letter of intent should be sent to:

Francisco O. Calvo, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: fc15y@nih.gov

3.B. Sending an Application to the NIH

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

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

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

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

Francisco O. Calvo, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: fc15y@nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

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

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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation 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/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

The Research Plan in applications for AMDCC Pathobiology Sites should include the indicated items in the following order:

Specific Instructions for Modular Grant applications

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Applicants must state a willingness to deposit all data with the AMDCC Coordinating and Bioinformatics Unit (CBU) in a timely fashion.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

New mouse models generated by the AMDCC will be made available to the greater scientific community and distributed by the Mouse Generation and Husbandry Core (MGHC).

Section V. Application Review Information

1. Criteria

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

The AMDCC Pathobiology Sites will be reviewed using both standard and additional criteria as outlined in Sections V.2. and 2.A.

The following will be considered in making funding decisions:

2. Review and Selection Process

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

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

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

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

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? Are the proposed specific aims for discovering the pathophysiologic mechanisms underlying these model(s) reasonable and novel? Are the methodologies chosen for characterizing the pathophysiologic mechanisms underlying these model(s) sufficient and appropriate? Are these parameters generally applicable to all mouse models of diabetic complications? Are the standards chosen to validate the model(s) for its relevance to a human diabetic complication or for testing therapy, prevention, early detection, or imaging appropriate and adequate?

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

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Have collaborations been established or consultants identified to provide the appropriate depth and breadth of scientific expertise required for the project? Will this team of investigators contribute unique skills to the overall Consortium?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? If advanced imaging techniques are proposed, is the instrument located behind an animal barrier?

2.A. Additional Review Criteria

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

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

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

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing. Program staff will be responsible for the administrative review of the plan for sharing research resources.

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

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 Principal Investigator will also receive a written critique called a Summary Statement.

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 14 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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.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 (U01), 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 above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for planning, organizing and administering the Pathobiology Site activities. He/She will participate as a voting member of the AMDCC Executive Steering Committee with PIs from the other AMDCC Pathobiology Sites, the Director of the Mouse Generation and Husbandry Core, the PI of the Coordinating and Bioinformatics Unit, and NIH staff. This includes planning, organizing and carrying-out administrative and research activities to serve the AMDCC, timely transfer of data to the CBU, and service on the Executive Steering Committee. The PI agrees to comply with any Consortium-wide policies established by the Executive Steering Committee.

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

2.A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. He/She will participate as a voting member of the AMDCC Executive Steering Committee, and will invite members of the External Advisory Board to serve. The NIH Project Scientist will help plan and carry-out AMDCC activities, and will participate in all reports. He/She will act as a liaison between the AMDCC and the NIH.

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 AMDCC will consist of multiple Pathobiology Sites, a Mouse Generation and Husbandry Core, and a Coordinating and Bioinformatics Unit; it will be guided by an AMDCC Executive Steering Committee and External Advisory Board.

Consortium Activities and Responsibilities
The Principal Investigator (PI) of the AMDCC Pathobiology Site must agree to be an active participant in Consortium-wide activities as deemed necessary by appropriate oversight committees.

Executive Steering Committee
Principal Investigators of AMDCC Pathobiology Sites must agree to participate in the Executive Steering Committee (ESC) of the AMDCC. The Executive Steering Committee meets monthly by teleconference and twice each year in person to encourage information exchange within the Consortium. The AMDCC Executive Steering Committee will consist of PIs from each of the AMDCC Pathobiology Sites, the Director of the Mouse Generation and Husbandry Core, the PI of the Coordinating and Bioinformatics Unit, and NIH staff. The ESC Chair will be chosen from among PIs of Pathobiology Sites (AMDCC) and may rotate annually. The ESC may form and charge other subcommittees as needed.

The purpose of the Executive Steering Committee will be to discuss and evaluate concerns and cooperative activities of the Consortium. The ESC may also establish Consortium-wide policies. If voting is necessary for an action item, individual PIs and NIH staff hold one vote each. The Executive Steering Committee will discuss and evaluate subcommittee and consortial activities and provide feedback to subcommittee leaders at least bi-annually, implement changes in subcommittee membership or direction if needed, and discuss and evaluate new projects and collaborative activities.

External Advisory Board (EAB)
The Principal Investigator of the AMDCC Pathobiology Site must indicate his/her intention to be responsive to recommendations provided by an independent External Advisory Board (EAB). The AMDCC EAB will meet annually in conjunction with one of the semi-annual meetings of the AMDCC Executive Steering Committee. At these annual meetings the EAB will review interim progress and provide an annual report and recommendations to the Executive Steering Committee and the NIH. The CBU will be responsible for organizing and providing minutes of these meetings.

Members of the EAB will be nominated by the Executive Steering Committee of the AMDCC in collaboration with the NIDDK and participating Institutes, and will be invited by the NIH. A chairman for the AMDCC EAB will be chosen from among the EAB members, who will be accomplished senior scientists from academia and industry with backgrounds in diabetes, diabetic complications, obesity, animal models, mouse genetics and technologies associated with mouse phenotyping. If voting is necessary for an action item, members of the EAB and the EAB chair hold one vote each. The AMDCC Executive Steering Committee will discuss implementation of EAB recommendations, plan a strategy and timeline for making these changes, and report back to the EAB in a timely fashion.

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 PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Awardees will also be required to submit an “AMDCC Annual Report” document. This document should not exceed 10 pages and will be made available to NIH staff, the AMDCC EAB, and the public via http://www.AMDCC.org.

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:

Chris Ketchum, Ph.D.
Division of Kidney, Urology and Hematology
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 647
Bethesda, MD 20892-5458
Telephone: 301-594-7717
Fax: 301-480-3510
Email: ck228s@nih.gov

Cristina Rabadan-Diehl, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 10186
Bethesda, MD 20892-7164
Phone: 301-435-0550
Fax: 301-480-2858
Email: cr60i@nih.gov

John D. Porter, Ph.D.
Channels, Synapses, and Circuits Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 2142 
Bethesda, MD 20892 (Rockville, MD 20852 for express/courier service)
Telephone: 301-496-1917
FAX: 301-402-1501
Email: jp477n@nih.gov

2. Peer Review Contacts:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: 301-594-8897
FAX: 301-480-3505
Email: fc15y@nih.gov

3. Financial or Grants Management Contacts:

Helen Ling
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd., Room 732
Bethesda, MD 20892-5456
Telephone: 301-594-8857
FAX: 301-480-3504
Email: hl12d@nih.gov

Owen Bobbitt
Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20892
RM 7134 MSC 7926
Telephone: 301 435-0184
Fax: 301-480-3310
Email: ob5i@nih.gov

Eddie Myrbeck
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Suite 3290, MSC 9537
Bethesda, MD 20892-9537 (Rockville, MD 20852 for express/courier service)
Telephone: 301-496-3938
FAX: 301-451-5635
Email: em180i@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.

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/archive/archive/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. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov/) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/publicaccess_Manual.htm).

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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to 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 PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 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.


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