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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)
National Institute of Allergy and Infectious Diseases (NIAID) (http://www3.niaid.nih.gov)

Title: Limited Competition: Continuation of the Clinical Islet Transplantation (CIT) Consortium (U01)

Announcement Type
This is a reissue of RFA-DK-04-004 and RFA-DK-04-005.

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

Request For Applications (RFA) Number: RFA-DK-09-501

Catalog of Federal Domestic Assistance Number(s)
93.847, 93.855, 93.856

Key Dates
Release Date: January 13, 2009
Application Receipt Date: March 19, 2009
Peer Review Date(s): May-June 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 2009
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: March 20, 2009

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
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose of this FOA

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Allergy and Infectious Diseases (NIAID) invite applications for Clinical Centers (CC) and a Data Coordinating Center (DCC) to participate in a consortium of investigators and institutions that will continue the implementation of established clinical studies of islet transplantation in patients with type 1 diabetes mellitus (T1D). The original Clinical Islet Transplant Consortium (CIT), established in FY 2004 under RFA DK-04-005 and RFA DK-04-005, has planned and initiated a program of single- and multi-center clinical trials in pancreatic islet transplantation for individuals with type I diabetes, with or without a prior kidney transplant. These trials are accompanied by metabolic and immunologic mechanistic studies. Successful applicants for the current funding opportunity (one DCC, together with up to 9 Clinical Centers (CCs)), will constitute the Clinical Islet Transplantation (CIT) consortium, the aim of which is to complete the existing CIT islet transplant studies. This effort is intended to result in an improved treatment of T1D and licensure of the human islet product.

The CIT Data Coordinating Center (CIT-DCC) will provide a broad range of support services for the CIT, including statistical, monitoring, and operational support. It will also assist with the preparation of DSMB reports, regulatory submissions, scientific manuscripts, and other reports and documents as needed to support the work and goals of the clinical centers in the consortium and/or as required by the NIH.

The CCs together with the DCC will continue the current CIT scientific agenda and complete the CIT studies that are currently under way (a list of studies is available at http://www.isletstudy.org). Additionally they will share information and resources that will advance the field of islet transplantation.

Research Objectives

Background

T1D is an autoimmune disease characterized by the destruction of the insulin-secreting beta cells of the pancreas by cytotoxic T cells. T1D can be difficult to control with currently available therapies. Life threatening and altering consequences are major problems for some patients with T1D including hypoglycemia, accelerated cardiovascular and peripheral vascular diseases, nephropathy, retinopathy, neuropathy, oral diseases and premature death. The incidence of T1D appears to be increasing worldwide. Although the disease may occur at any age, onset peaks prior to twenty years of age. In some populations, approximately one percent of all newborns will develop T1D during their lifetime.

Islet transplantation as a therapy for T1D has been an important focus of NIH support, and significant progress has occurred in recent years. In particular, the success of the "Edmonton Protocol" for islet transplantation in freeing individuals with T1D from the need for insulin therapy has established islet transplantation as an alternative therapy for those T1D patients whose disease cannot be effectively managed with current methods of exogenous insulin administration. However, significant obstacles remain for development of islet transplantation as a treatment for T1D in the general population, most notably the toxicity associated with current regimens of immunosuppression and islet administration and the limited supply of human cadaveric islets, which is sufficient for only a small fraction of the people who could potentially benefit from this therapy. The recent successes in islet transplantation provide additional impetus for research to develop methods to attain an unlimited supply of islets for transplantation; to improve methods for harvesting pancreata and isolating islets; to improve techniques for the administration of transplanted islets; and to develop approaches to minimize the toxicity of immunotherapy required for transplantation.

Objectives and Scope

The purpose of this FOA is to support CCs and a DCC for an established program of cooperative clinical trials with associated mechanistic studies in human islet transplantation. Clinical studies (see http://www.isletstudy.org/.) including single/multiple-center pilot studies investigating an innovative approach and multi-center pivotal (phase III) studies have been designed to evaluate/accomplish:

1. Increasing the efficiency of islet transplantation, with the goal of achieving successful single-donor islet transplantation.

2. Improvements in immunotherapy to reduce toxicity, recurrent autoimmunity and allograft rejection.

3. FDA licensure of the human islet product.

In association with ongoing clinical trials, the CIT has designed mechanistic studies to enhance understanding of rejection, engraftment and/or survival of islets in the setting of islet transplantation.

The Data Coordinating Center for the consortium will continue providing support in the following areas:

1) Study Design, Conduct, Analyses, and Publications - The DCC will provide statistical leadership for the consortium. It will oversee implementation of the current clinical trials and implement the statistical analysis plans that have been submitted to the FDA, and will also be responsible for assisting with all updates to the protocols and manuals of operation ; implementation and, where necessary, modification of the existing data safety and monitoring plans; collaborating with the NIAID Regulatory and Medical staff to implement the existing procedures for reporting of Serious Adverse Events; performing interim analyses of safety and efficacy for protocol teams, NIH, and the Data Safety and Monitoring Board (DSMB); generating executive summaries of study results for use by the protocol team, NIH, and collaborators; conducting the final analyses and participating on publication writing teams; performing cross-protocol or cross study analyses utilizing data from multiple sources within and external to the consortium; producing study monitoring reports for the consortium and NIH; and conducting analyses and summaries for annual and interim reports for NIH-sponsored Investigational New Drug Applications, in cooperation with the NIAID Regulatory and Program staff or Support Contractor (see below).

2) Data Management Provide central registration and randomization (as required by study protocols) for all study subjects; develop/modify case report forms and standardized criteria for clinical endpoint verification; maintain, design and implement as needed systems for the efficient tracking and transfer of clinical and laboratory data (including quality assurance and specimen tracking) to the central database; provide data management training to the clinical sites and laboratories; provide CRF notebooks to collaborators; provide for central storage, security, processing and retrieval of study results; and prepare selected public access databases.

3) Site Monitoring Through a subcontract Clinical Research Organization(s) initiate, monitor, and close out clinical sites, pharmacies, and laboratories to assure Good Clinical/Laboratory Practice (GCP/GLP); together with NIAID regulatory staff, train site personnel on GCP/GLP/GTP compliance and on the policies and procedures established by the NIH, the Food and Drug Administration (FDA), and the Office of Human Research Protections (OHRP); audit clinical, pharmacy, and laboratory sites, as well as islet facilities, as necessary; and provide reports to the NIH and the Steering Committee on monitoring and audit findings and training activities.

4) Administrative Support Organize meetings and teleconferences; provide core laboratory support and coordination, including specimen handling; distribute study drugs and supplies.

5) Regulatory Requirements The DCC will work in concert with the NIAID Regulatory Affairs Staff and/or Support Contractor and NIH staff by providing them with clinical study data, reports, and other support as required for Adverse Event Reporting and IND submissions

It is expected that the successful DCC applicant will bring a range of experiences and perspectives to this consortium that will inform group decisions and accelerate the pace of progress toward general clinical applicability of islet transplantation for the treatment of T1D.

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 NIH Cooperative Agreement (U01) award mechanism(s).

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". There are no plans to extend the consortium beyond the current funding opportunity.

2. Funds Available

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:

* Only foreign organizations currently supported under RFA-DK-04-005 are eligible to apply.

1.B. Eligible Individuals

Any individual 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.

Other CC PD/PI requirements include: (1) for clinical centers, the applicant must be an islet transplant program that meets the clinical requirements for study participation as posted on the CIT website (http://www.isletstudy.org). For North American clinical centers, the applicant must also be an islet transplant program the meets the manufacturing requirements for study participation as posted on the CIT website (http://www.isletstudy.org).

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

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

Renewals. Renewal applications are permitted in response to this FOA Information.

Number of Applications. Applicants may not submit more than one application.

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: [email protected].

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:

In addition, for applications from foreign organizations:

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.

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
Application Receipt Date: March 19, 2009
Peer Review Date(s): May-June 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September, 2009

3.A.1. Letter of Intent

A letter of intent is not required for the funding opportunity.

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 O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and digestive and Kidney Diseases
National Institutes of Health
6707 Democracy Boulevard
Two Democracy Plaza Rm 752, MSC 5452
Bethesda, MD 20892-5452
Courier use 20817
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: [email protected]

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 and Information

The CC applicant must address the following responsibilities and requirements:

1. Applications for the CCs should demonstrate their accomplishments related to their participation within the CIT (e.g., recruitment of subjects, transplantation of patients, committee membership or chairmanship, protocol development, publications, etc.). In addition, there should be a discussion of any impediments to progress that have occurred in enrolling and/or transplanting patients.

2. Each CC submitting an application in response to this FOA must provide a one page summary of their site specific protocol and mechanistic studies and evidence of their ability to carry out the protocols already approved the CIT. The applicant must justify the continued relevance of this research protocol and describe its potential impact on the field of islet transplantation; scientific advances that have occurred over the last 5 years that are relevant to this research protocol should be addressed.

3. The CC application must provide detailed plans for future subject recruitment and retention in all of the CIT studies in which the site participates. Each application should describe specific barriers to the retention of the patient population at their clinical sites and discuss how they plan to address these barriers.

4. The CC applicant must also provide a listing of all islet isolations performed using the CIT Batch Record and their results.

5. The CC applicant must specifically describe contributions made to the consortium by individuals at the applicant site during the first 5 years of the CIT consortium.

6CCs must provide information regarding past contributions to and future plans for involvement with operational committees of the CIT (e.g. Recruitment, Publications, Manufacturing, etc.) and the establishment of uniform procedures and policies.

7. There should be evidence of strong institutional support for the CC, including adequate space in which to conduct clinical and research activities and office space for staff. Each CC applicant must have access to an NIH-supported General Clinical Research Center (GCRC), Clinical and Translation Science Award (CTSA) site or an equivalent facility to support inpatient study costs. An equivalent GCRC facility is defined as dedicated inpatient beds staffed by personnel experienced in the conduct of research protocols and in performing diabetes care, with institutional commitment to provide such beds, along with support for outpatient testing. A letter of agreement from either the GCRC, CTSA or GCRC equivalent Program Director or PI should be included with the application. Resources for patient care and follow-up, including personnel, space, and facilities for patient follow-up including metabolic monitoring should be described. Letters from institutional officials should describe any other institutional support that will be available for the CIT.

8. An organizational structure for the CC should be set forth in the application, delineating lines of authority and responsibility for dealing with problems. The application must reflect adequate time commitment of personnel. The minimum time commitment for the PI is 20%. Personnel for support of the clinical trials must include a Clinical Trial Coordinator (100%) and other personnel required at the applicant institution and other contributing sites to conduct the planned clinical and mechanistic studies. PI and the Institution(s) should indicate his/her willingness to participate in a per patient basis for cost reimbursement.

9. Budget Information: Applicant should request support for the PI, a trial coordinator and other personnel as outlined above. In addition the budget for all costs (travel; equipment; supplies; screening; patient care; islet procurement and isolation; and on site laboratory tests) associated with the clinical and mechanistic studies should be included. Costs for travel to steering committee meetings should be estimated on one steering committee meeting per year. CC applicants should prepare estimated budgets for three 12-month periods including any estimated carryover from this initiative’s initial funding period. Requested additional funds should not exceed $4.5 million total cost.

The DCC applicant must address the following responsibilities and requirements:

1. The DCC application should describe accomplishments, including its operational infrastructure (committees, procedures for coordination and communication, etc). It is expected that the PI of the DCC will carry out a significant leadership role in the consortium2. The application must reflect adequate time commitment of personnel. The minimum time commitment for the PI is 20%.

3. Budget Information: The application should include budgets for three 12-month periods including any estimated carryover. Requested additional funds should not exceed $12 million total cost.

4. Other responsibilities/requirements include:

Requirements and Responsibilities for both the DCC and CCs:

The CIT will continue to be a collaborative effort that will require frequent interactions of awardees among themselves and with the NIH. Applicants must explicitly indicate their willingness to:

1. Participate in Steering Committee meetings (expected to occur in person at least once a year in or near the Bethesda, MD area and teleconferences at least monthly, as needed), site visits required by the NIH, and other CIT-related telephone conference calls;

2. Cooperate with other awardees in the further development and design or modification of research protocols, and cooperate with other awardees in carrying out approved research protocols;

3. Abide by common definitions; common methods for patient selection and enrollment; and common protocols, procedures, tests, and reporting forms as chosen by majority vote of the Steering Committee;

4. Actively seek to implement each site specific and consortium-wide protocol for which the site is selected for participation;

5. Comply with all study policies and quality assurance measures approved by the Steering Committee;

6. Agree to oversight of the study by a Data and Safety Monitoring Board (DSMB);

7. Transmit study data to the Data and Coordinating Center in a timely and accurate manner (Clinical Centers only);

8. Report all adverse events in accordance with procedures established by the NIH and CIT policies;

10. Cooperate with other awardees in the publication of study results and the eventual release to the scientific community of study procedures and other resources;

11. Serve on and chair subcommittees and protocol committees as assigned by the steering committee;

12. Accept the Cooperative Agreement Terms and Conditions of Award in Section VI.2.A Award Administration Information .

Research Plan Page Limitations

The research plan is limited to 20 pages.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only, and include five identical CDs in the same package with the application. If submitting CDs it is not necessary to include a paper appendix. (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/.

The DCC application should include an overall sharing plan for data generated during the funding of the CIT. The plan should indicate specifically what will be shared, with whom it will be shared (including the NIDDK Data Repository), when it will be shared, by what means it will be shared, and what conditions will apply to recipients of shared data. The CCs will work with the DCC through the steering committee to implement a final sharing plan. This plan must be approved by the NIH before awards will be issued under this FOA.

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

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 (NIDDK) 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:

The following will be considered in making funding decisions:

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 meritorious 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? If problems were previously encountered in the implementation of this research, has the applicant described those problems and the approach to resolving them?

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)? Additionally, do the specific competence and previous experience of the professional, technical and administrative staff of the CC or the DCC increase the likelihood the goals of the research plans will be achieved? Are the expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator and co-investigators at the DCC, and the time they plan to devote to the effective coordination of the CIT appropriate? Have individuals from the applicant site made substantive contributions to achieving the aims of the consortium during the first 5 years of funding?

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? Is there evidence of adequate facilities, space, and resources for the work proposed including evidence of an appropriate organizational structure and institutional support? Do the collaborative arrangements within the proposed Network enhance the productivity of the CC or DCC? Are the facilities, equipment, environment and organizational structure of the DCC adequate to effectively coordinate the CIT activities in implementing the protocols, data collection and providing for specialized methodologies and plans for collecting and distribution of biospecimens to the central labs and NIDDK repositories adequate?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the priority score.

COMMITMENT: Is there evidence of commitment to continue to conduct the approved studies of the CIT? Is there evidence of a strong willingness to work cooperatively and to participate in all aspects of a cooperative network including service on subcommittees and authoring publications and proposals?

Review of the CC applicants will also be based on the following specific criteria:

1. Recruitment and Retention: Has there been adequate progress in recruiting and transplanting patients? Is there evidence that the CC will be able to meet the planned recruitment goals and retention of research subjects in the CIT approved studies. Have they demonstrated their willingness and ability to recruit and retain these patients in clinical trials and epidemiological studies?

2. Data and Sample Management: Is there an adequate plan to ensure the timely and accurate transmission of study data to the DCC and patient samples to the central labs and the NIDDK repositories?

Review of the DCC application also will be based on the following specific criteria:

1. Has the DCC demonstrated an understanding of the scientific, statistical, logistical, and technical issues underlying the CIT single and multi-center studies and knowledge necessary to lead in the areas of biostatistical study design, statistics, logistics, data acquisition and management, identification of and coordination with drug distribution centers and serum/tissue/data repositories, handling of laboratory specimens, quality control, data analysis, and consortium coordination?

2. Are the proposed plans for acquisition, transfer, management, and analysis of data, quality control of data collection and monitoring, and overall coordination of the CIT adequate?

3. Is there the ability to develop or modify the Data Safety and Monitoring Plan, Manuals of Operations and Case Report Forms for the multiple CIT sites and studies?

4. Is there the ability to support the NIAID in preparing and filing the necessary regulatory documents?

2.A. Additional Review Criteria:

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

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

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

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan 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.

Applications from Foreign Organizations: Whether the project presents 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 will be assessed

2.C. Resource Sharing Plan(s)

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

The DCC application should include an overall sharing plan for data generated during the funding of the CIT. The plan should indicate specifically what will be shared, with whom it will be shared (including the NIDDK Data Repository), when it will be shared, by what means it will be shared, and what conditions will apply to recipients of shared data. The CCs will work with the DCC through the steering committee to implement a final sharing plan. This plan must be approved by the NIH before awards will be issued under this FOA.

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 Notice of Award 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 Notice of Award will be mailed to the business official.

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

2. Administrative and National Policy Requirements

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

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

The PI will have primary responsibility for defining the research objectives, approaches and details of the projects within the guidelines of the RFA and for performing the scientific activity. Specifically, PIs have primary responsibility as described below.

Each PI will be a voting member of the Steering Committee and will be required to participate in all Steering Committee activities and to follow the policies and procedures that are developed by the Steering Committee. The CC PIs will be required to provide primary study data to the Coordinating Center for management, quality control, and analysis. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The collaborative protocol and governance policies will call for the continued submission of data centrally to the CIT-DCC for a collaborative database; the submission of copies of the collaborative data sets to each PI upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data (if any) and records of individuals. The NIH Program Directors, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

The DCC will be involved in collaborations with the NIH and the CCs during all phases of the trial and will maintain or contract with the NIDDK Biosample Repository for stored samples. In addition, the DCC will coordinate with the NIDDK Data Repository to prepare the data for eventual archiving and distribution. Thus, the DCC awardee is expected to work cooperatively with Clinical Centers and sponsoring organizations and oversee the implementation of and adherence to a common protocol, as well as assure quality control of the data collected and storage of collected biologic specimens. In addition to organizing and attending regular meetings (including conference calls), the CIT-DCC will be expected to maintain close communications with the NIH Scientific Coordinators, and the CC PIs.

PIs are expected to publish and to publicly release and disseminate results, data and other products of the study, concordant with the study protocol and governance and the approved plan for making data and materials available to the scientific community and the NIH. Support or other involvement of industry or any other third party in any study performed by the Consortium -- e.g., participation by the third party; involvement of project resources or citing the name of the project or the NIH support; or special access to project results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only in the context of a Clinical Trials Agreement with the NIH.

Upon completion of the project, the DCC is expected to put all study intervention materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NIDDK/NIAID, for the conduct of research at no charge other than the costs of reproduction and distribution. Indeed, NIH policy requires that investigators 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/grants/policy/nihgps; Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice, December 1999 (http://www.ott.nih.gov/policy/rt_guide_final.html)]. It is expected that the specimens and data collected in projects funded by this RFA will eventually be made available to the broader scientific community, after a proprietary period.

PIs acknowledge in their approved "Sharing Plan" that they will share the specimens and data collected with the wider scientific community, through eventual transfer of these materials to the NIDDK Central Biosample and Data Repositories or through another mechanism determined by NIH. Evaluation of the Non-competing Grant Progress Report (PHS 2590) will include assessment of the effectiveness of research resource release.

The PIs' responsibilities regarding Steering Committee membership, protocol development and conduct, and data coordination and management are described under Collaborative Responsibilities.

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

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

NIH Program Directors will be assigned to perform normal program stewardship responsibilities for this award. The Government, via the NIH Program Directors, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. NIH Staff may use information obtained from the data for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Program Review:

The NIH Program Directors, together with the CIT-DCC and the Steering Committee, will review the progress of each participating institution through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting.

Monitoring Study Performance:

The NIH Program Directors and the CIT-DCC will assist the Steering Committee in the development of mechanisms and procedures for monitoring study performance. This includes participation in periodic on-site monitoring of compliance with protocol specifications, quality control and accuracy of data recording, and patient accrual. The monitoring plan will incorporate any relevant regulatory requirements.

The NIH reserves the right to terminate or curtail any study or any individual award in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (b) substantive changes in the consensus protocol to which the NIH does not agree, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, (d) human subject ethical issues that may dictate a premature termination, (e) evidence of study lack of efficacy, or (f) budgetary insufficiency.

Organizational Changes:

Certain organizational changes require the prior written approval of the NIH Program Directors. These changes include the addition or replacement of a physician, scientific investigator, affiliate, component, or research base that is associated with this study. A change in the PI, or in any key personnel identified on the Notice of Award, must have the prior written approval of the NIH Grants Management Specialist in consultation with the NIH Program Director.

The NIH Program Director may also serve as the NIH Scientific Coordinator.

NIH Scientific Coordinator:

NIH staff assistance as NIH Scientific Coordinators will be provided by the Islet Transplantation Program Director, DDEM, NIDDK, and the Chief of the Clinical Transplantation Section, DAIT, NIAID or their designees. These NIH Scientific Coordinators and/or their designees will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below.

During performance of the award, the NIH Scientific Coordinators, with assistance from other scientific program staff who are designated based on the research topic and their relevant expertise, may provide appropriate assistance, advice, and guidance by: participating in the design of the activities; advising in the selection of sources or resources (e.g., determining where a particular reagent can be found, or assay performed); coordinating or participating in the collection and/or analysis of data; advising in management and technical performance; or participating in the preparation of publications. The Scientific Coordinators and NIH Regulatory Staff will serve as a liaison/facilitator between the PI, pharmaceutical and biotech industries, and other government agencies (e.g., FDA, USDA, CDC) and will serve as a resource of scientific and policy information related to the goals of the PI’s research. However, the role of the NIH will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus, and that the NIH Program Directors will participate in this process. The NIH Scientific Coordinators will serve as voting members of the Steering Committee and will participate in all Committee activities.

Regulatory Affairs:

The NIH Regulatory Affairs staff, assisted by the staff of the CIT-DCC and the NIAID Regulatory Contractor, will be responsible for preparing all regulatory documents required by the Food and Drug Administration, and will provide to the PI the guidance and assistance necessary to ensure that compliance with FDA regulations is maintained. The NIH regulatory affairs staff will initiate and participate in all communication with FDA representatives.

Site Support:

NIH Scientific Coordinators or their designees and/or CIT-DCC staff (or contractors) will visit all sites prior to patient enrollment, to carry out site education with regard to protocol requirements and data submission procedures. NIH Scientific Coordinators and DCC staff will meet at least monthly, by teleconference, with the site coordinators for each study, to discuss recruitment issues and study operations.

Protocol Implementation:

As members of the Steering Committee, the NIH Scientific Coordinators will serve as a resource with respect to the implementation of the protocols and will, along with the CIT-DCC, assist the Steering Committee in protocol implementation.

Data Coordination and Management:

The NIH Scientific Coordinators and the CIT-DCC will provide technical assistance and data management services to the participating institutions with respect to quality control, uniformity of data collection, management of the collective database, and data analyses.

Publication and Presentation of Study Findings:

The NIH Scientific Coordinators may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the study to the investigator community and other interested scientific and lay organizations. Co-authorship by the NIH Program Directors will be subject to approval in accordance with NIH policies regarding staff authorship of publications resulting from extramural awards.

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 (optional)

Steering Committee:

A Steering Committee serves as the main governing body of the cooperative research program. The Steering Committee will review all concepts for scientific merit and feasibility; review all protocols prior to implementation; review all public presentations of CIT results and manuscripts, posters, and abstracts prior to publication; review compliance with protocol requirements; define subcommittees; develop study policies; receive and act upon reports of subcommittees; and review matters relevant to administrative, financial, medical, legal, and ethical considerations of studies. The Steering Committee will maintain surveillance of the CIT performance and, together with the NIH, is responsible for the addition or deletion of CCs.

The Chairperson of the Steering Committee is responsible for the overall administration and science of the CIT activities by providing leadership for the steering committee activities described above. He/she will, together with the leadership of the DCC and the NIH Scientific Coordinators, schedule steering committee and investigator meetings; establish the agenda for those meetings; and monitor the work of the subcommittees.

At a minimum, the Steering Committee will be composed of the following individuals: the PI of the CCs; the PI of the CIT-DCC; the chair of the Mechanistic Studies Subcommittee (see below); and the NIH Scientific Coordinators (the Islet Transplantation Program Director, DDEM, NIDDK; and the Chief of the Clinical Transplantation Section, DAIT, NIAID or their designees). Additional members, voting or non-voting, may be added to the steering committee by majority vote of the Steering Committee; non-voting members may be added at the discretion of the NIH Scientific Coordinators. All major scientific decisions will be determined by the Steering Committee, with each CC PI, the NIH Scientific Coordinators, and the PI of the CIT-DCC having one vote.

The Steering Committee will meet in person at least once annually and by teleconference at least monthly. Additional meetings by teleconference will be scheduled as needed, with need determined by the Steering Committee Chair and the NIH Scientific Coordinators. The Steering Committee elects a Chairperson from among the Steering Committee members; the NIH Scientific Coordinators and the PI of the CIT-DCC are not eligible to be the Steering Committee Chair. Each Steering Committee member will be expected to participate in all Steering Committee activities, e.g., meetings, conference calls, special subcommittee activities, etc. as may be necessary.

The Steering Committee will have primary responsibility for implementing the clinical protocols, approving the design and implementation of all mechanistic studies (via the Mechanistic Studies Subcommittee), facilitating the conduct and monitoring of all clinical trials and mechanistic studies, analyzing and interpreting study data, and reporting study results. Studies will not be approved if the NIH or the Steering Committee determines that it will not be feasible to accrue patients within the specified time frame.

Executive Committee:

An Executive Committee comprised of the Steering Committee Chair, the PI of the CIT-DCC, and the NIH Scientific Coordinators will be convened to effect management decisions required between Steering Committee meetings, as needed for efficient progress of the studies.

Investigational Protocols:

One PI or subcommittee will take the lead responsibility for implementing each individual protocol, with the assistance of the CIT-DCC and NIH Scientific Coordinators. The Steering Committee will provide input and will be responsible for oversight of protocol development. Any decision to discontinue a protocol will be determined by the NIH, a vote of the entire steering committee and/or review by the DSMB.

Mechanistic Studies Subcommittee:

The Steering Committee shall appoint a Mechanistic Studies Subcommittee to review and approve or modify proposed mechanistic studies. Each PI shall select one representative from his/her consortium as voting members of the Mechanistic Studies Subcommittee. In addition, the NIH Scientific Coordinators or their designees, shall serve as voting members. The Mechanistic Studies Subcommittee may ask the Steering Committee to appoint additional Mechanistic Studies Subcommittee members if additional expertise in a specific area is needed. The Mechanistic Studies Subcommittee shall elect a Chair from among its non-Federal members. The Chair shall serve as a voting member of the Steering Committee. The Subcommittee will meet at least twice yearly and its members will be expected to participate in all meetings, conference calls, and other Subcommittee activities.

Performance Subcommittee:

The performance subcommittee will develop a set of performance criteria to evaluate accrual, data submission, and protocol compliance at each participating institution in the consortium, including institutions participating in consortium arrangements. These criteria, after approval by the Steering Committee, will form the basis for determining continued participation of each site in the consortium, on a yearly basis.

Data and Safety Monitoring Board (DSMB):

An independent DSMB, appointed by the NIH, will review CIT studies at least annually and report their findings to the NIH Program Directors. Clinical protocols and mechanistic studies will be subject to review by the DSMB, in an advisory capacity, prior to implementation. The DSMB review will focus on the safety, ethics, and scientific and statistical integrity.

Data Coordination and Management:

Data Coordination and Management will be carried out by the CIT-DCC. Each participating institution will be responsible for providing primary study data to the NIH via the CIT-DCC for management, quality control, and analysis, using procedures and standards determined by the Steering Committee and the CIT-DCC. The NIH will provide, via its program staff and the CIT-DCC, the following: technical assistance and data management services to the participating clinical institutions with respect to quality control, uniformity of data collection, management of the collective database, and data analysis; centralized data collection and management; and quality assurance. Specific analyses to be performed will be directed by the Steering Committee or the NIH Scientific Coordinators. The results of those analyses will be delivered to the Steering Committee. The Steering Committee is responsible for determining how the results are interpreted, whether the results should influence ongoing data collection, and how the findings should be disseminated. In the event of a specific safety concern, the DSMB may request specific analyses from the DCC. All participating sites will have access to all data originating from their sites. The awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies.

Publication and Presentation of Study Findings:

Timely publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of the participating institutions and NIH support. Policies for directing analyses of aggregate and site-specific data will be developed by the Steering Committee. Review and approval by the Steering Committee will be required for all analyses prior to publication or presentation according to criteria that will be developed by the Steering Committee.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

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:

Thomas L. Eggerman M.D., Ph.D
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 697
Bethesda, MD 20892-5460
Telephone: (301) 594-8813
FAX: (301) 480-3503
Email: [email protected]

Nancy D. Bridges, M.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
6610 Rockledge Drive, Room 3039
Bethesda, MD 20892-6603
Telephone: (301) 451-4406
FAX: (301) 480-0693
Email: [email protected]

2. Peer Review Contacts:

Francisco O. Calvo, Ph.D
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
Telephone: (301) 594-8885
FAX: (301) 480-3505
Email: [email protected]

3. Financial or Grants Management Contacts:

Craig E. Bagdon, MPA
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 721
Bethesda, MD 20892-5460
Telephone: (301) 594-2115
FAX: (301) 594-9523
Email: [email protected]

Victoria P. Connors
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700 B Rockledge Drive, Room 2122
Bethesda, MD 20892
Telephone: (301) 402-5065
FAX: (301) 493-0597
Email: [email protected]

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

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

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (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.

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NIH Funding Opportunities and Notices


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