Part I Overview Information

Department of Health and Human Services

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

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

Title: Ancillary Studies in the Natural History of Acute Kidney Injury (U01)

Announcement Type

New

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

Request For Applications (RFA) Number: RFA-DK-07-009

Catalog of Federal Domestic Assistance Number(s)
93.849

Key Dates
Release Date: October 5, 2007
Letters of Intent Receipt Date: November 26, 2007
Application Receipt Date: December 20, 2007
Peer Review Date(s): March-April 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 1, 2008
Additional Information To Be Available Date (Url Activation Date): December 20, 2008
Expiration Date: December 21, 2007

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 and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. 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

This FOA issued by the NIDDK solicits research grant applications to conduct clinical studies examining the natural history of Acute Kidney Injury under a multicenter cooperative agreement. The primary objective of this FOA is to establish an Acute Kidney Injury Natural History Consortium comprised of 3-5 PCCs and one DCC. Each PCC will be expected to follow 200-600 patients with Acute Kidney Injury and a similar number of control subjects for up to 4 years for the development or worsening of chronic kidney disease and selected cardiovascular complications. The PCCs must consist of ancillary studies to ongoing clinical studies or trials of Acute Kidney injury or related topics. The secondary objective of the FOA is to create a central repository to preserve the data and biological samples to share with the scientific community for future secondary analyses and biomarker studies.

Pertinent background information that establishes the need for the research

Acute Kidney Injury is a common complication following ischemic, septic, and/or toxic insults to the kidney and is associated with substantial morbidity and mortality (up to 50% mortality). Recent studies have suggested that the incidence of Acute Kidney Injury has increased dramatically over the past 20 years. Whereas chronic kidney disease is well known to predispose to all forms of Acute Kidney Injury, recent animal and epidemiologic studies have suggested that Acute Kidney Injury can worsen and contribute to the development of chronic kidney disease leading to end-stage renal disease. This may be especially critical in the late stages of chronic kidney disease, with rapid progression to chronic dialysis. Despite some advances in our understanding of the pathophysiology and epidemiology of Acute Kidney Injury, real breakthroughs in treatment and management of the disease have not been achieved because of the lack of informative biomarkers and uncertainty about the natural history of Acute Kidney Injury. Several biomarker, clinical research, and clinical trials are currently starting or underway. Unfortunately, these studies are designed to only follow patients for a brief period of time; longer term long-term follow-up was precluded because of lack of funding. Hence, this FOA seeks to leverage and extend current investments by NIH and others to establish the natural history of AKI.

Objectives and Scope

This FOA seeks to establish an Acute Kidney Injury Natural History Consortium consisting of 3-5 PCCs and a single DCC. The primary objective of the Consortium is to follow the natural history of patients with Acute Kidney Injury after they finish the acute phase of their illness, and compare with concurrent relevant control patients. The proposed study MUST be ancillary to an ongoing clinical study of either of timed renal (after cardiopulmonary bypass, nephrotoxin administration), or more complex un-timed forms of AKI (occurring in the ICU, or from sepsis or multiple insults). The proposed study may involve the entire cohort participating in the ongoing clinical study or selected nested subset(s) of the participants, depending on the scientific questions posed and the sample size required to answer them. The PI of the proposed ancillary study need not be the PI of the parent study; however, the parent study must approve of the ancillary study and must agree to share data with the Acute Kidney Injury Natural History Consortium.

The PCCs in the Consortium will be expected to propose and participate in multiple common protocols that will be conducted in all PCCs. Applicants must be willing to work collaboratively in the development and implementation of protocols, as needed. The topics of these protocols will be decided and prioritized cooperatively by the Consortium SC after review and approval by the Scientific Advisory Committee (SAC).

The secondary objective of the Consortium is to establish a central repository to preserve the data and biosamples for future biomarker studies and secondary analyses by the research community.

Project Organization

The Clinical Research on Natural History of Acute Kidney Injury Consortium will be funded as a cooperative agreement consisting of 3-5 PCCs, a DCC and the NIH (NIDDK along with any other co-sponsoring NIH ICs). The responsibilities of each component of the Consortium are described below:

I. Participating Clinical Centers (PCC):

The PI at each PCC will be responsible for proposing protocols, and participating in their overall development, estimating the costs of protocols, conducting the research, assuring quality of participant management and protocol adherence, assuring the accurate and timely transmission of data collected to the DCC, and disseminating research findings. The PCCs are also expected to transfer appropriate baseline and outcome data from the parent grant in a timely fashion. The PCC should demonstrate both clinical science excellence and expertise in the assessment and/or management of Acute Kidney Injury and a proven ability to recruit and follow patients with Acute Kidney Injury.

II. Data and Coordinating Center (DCC):

The DCC will provide assistance in the following areas:

III. NIH:

The NIDDK, with other participating NIH ICs, will oversee the organization of the Consortium and thus will be substantially involved with the awardees in a partnership. The NIDDK Project Scientist will have significant scientific involvement with the awardees and administrative duties, monitor patient recruitment and retention, study progress, ensure disclosure of conflicts of interest, and ensure adherence to NIDDK policies. NIDDK will appoint the Study Chair (who may be from one of the applicant organizations or external to the Natural History of Acute Kidney Injury Consortium) and all members of the SAC. The NIH and Study Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Natural History of Acute Kidney Injury Consortium activities and operations.

IV. Steering Committee (SC):

The SC will be the main governing body of the Natural History of Acute Kidney Injury Consortium. Voting members of the SC include, at a minimum, the Study Chair, the PIs of the PCCs and of the DCC (or their designated alternate), and the NIDDK Project Scientist. The Study Chair will be appointed by the NIDDK. The Study Chair will plan the Natural History of Acute Kidney Injury Consortium activities, oversee its functions, conduct SC meetings, and cast tie-breaking votes in that committee. The SC will develop and ensure compliance with Natural History of Acute Kidney Injury Consortium policies and procedures, identify and prioritize strategies for investigation, evaluate protocols proposed by the PCCs, and develop common protocols for submission to the SAC for approval. The SC will ensure that studies are properly conducted and monitored, that data are appropriately analyzed and interpreted, and that study results are reported in the scientific literature in a timely manner. The SC may meet in-person as often as three to four times in the first 12 months of the study, and two to three times per year thereafter. All major scientific decisions will be determined by majority vote of the SC.

V. Scientific Advisory Committee (SAC):

NIDDK will establish a SAC in accordance with NIH policies to ensure data quality and participant safety and to provide independent advice to the NIDDK regarding progress and the appropriateness of continuing each study. The SAC members will be selected by NIDDK and will report to the Director, KUH.

The SAC (with additional ad hoc scientific and/or clinical experts as needed) will also evaluate protocols proposed by the SC. The recommendation of the SAC will be based on the importance of the question to be addressed, scientific merit of the experimental design and approach, feasibility, appropriateness for the Consortium and consistency with NIDDK missions and policies. The SAC will provide a written report of each proposal and a final recommendation to the NIDDK. APPLICANTS SHOULD NOT NOMINATE PROSPECTIVE SAC MEMBERS IN THEIR APPLICATIONS.

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

The NIH 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 FOA is a one-time solicitation. At this time, it is not known if this FOA will be reissued. Future renewal applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures.

2. Funds Available

NIDDK intends to commit approximately $2 million total costs (direct plus indirect) in FY2008 to support the Consortium comprised of 3-5 PCCs and one DCC. The total project period for the Consortium is five years.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC 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 support.

2. Cost Sharing or Matching

Not applicable.

The most current NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

The study proposed by Clinical Centers must be ancillary to an ongoing clinical study funded by the NIH. The PI of the parent study may also be the PI of the proposed ancillary study.

Section IV. Application and Submission Information

1. Address to Request Application Information

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

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed 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 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
Letters of Intent Receipt Date: November 26, 2007
Application Receipt Date: December 20, 2007
Peer Review Date(s): March-April 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 1, 2008

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.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone: (301) 594-8885
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.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone: (301) 594-8885
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.

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 PI in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing 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/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

Applications may exceed the 25 page limit to a maximum of 35 pages.

The proposed application should include the rationale, inclusion/exclusion criteria, primary and secondary outcomes, recruitment and retention rates, plans on how to re-contact the patients in the event that the parent study has already completed recruitment prior to the initiation of the award, event rates, power calculations, and evidence of compliance to the protocol. All PIs MUST provide documentation of permission from the parent study to use the patient cohorts, data, and biological materials of the parent study. The letter should provide examples of baseline and outcome data and biological materials to be shared, along with timelines for timely sharing of data and samples. The proposed study may involve the entire cohort participating in the ongoing clinical trial or selected subsets of the participants, depending on the scientific questions posed and the sample size required to answer them.

NOTE: For the purposes of this FOA, the PIs are requested to use the Acute Kidney Injury Network (AKIN) criteria for the definition of Acute Kidney Injury)

The application should include a clear description of the formal organizational structure of the consortium, including lines of authority and responsibility, with particular attention to the relationship of the organizational structure to the consortium's major objectives. Plans for interaction of the organizational elements should be described clearly.

Plan for Sharing Research Data

All investigators responding to this funding opportunity are expected to share research data and the application must include a statement that data will be shared.

NIDDK expects that baseline and outcome data from the parent study will be transferred to the AKI Natural History Consortium DCC in a timely fashion. In addition, the NIDDK has established Central Biosample, Genetic and Data Repositories for the archival and storage of data and biosamples. All samples and data transferred to the repositories will be under the custodianship of the NIDDK, although the study ’s SC will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. The PCCs will submit the samples and data to the NIDDK repository via the DCC and the study is expected to put all study design 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, for the conduct of research at no charge other than the costs of reproduction and distribution.

Sharing Research Resources

NIH policy expects that grant 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/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.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.

Section V. Application Review Information

1. Criteria

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to this 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?

PCC

How appropriate are the design and protocol(s) of the proposed strategy for each PCC? Is there adequate rationale/justification for the proposed end points and sample size(s)? Are power calculations included? Has the applicant provided sufficient information about the available participant population and convincingly described strategies likely to be successful in recruitment and retention for the proposed study. Do the applicants show an understanding of how joint collaborative activities can be conducted in the Natural History of Acute Kidney Injury Consortium and that it will be a group decision of the SC to actually engage in any particular proposed collaborative activity. Is the research plan of the PCC applicant flexible enough to accommodate further refinement and integration with other efforts?

DCC

Is there demonstrated evidence of an ability to address the complex scientific, statistical, logistical, and technical needs and issues underlying multi-center clinical studies? What is the potential for effective leadership in study design and statistics, data acquisition and management, data quality control, data analysis, handling and quality control of laboratory specimens, and Natural History of Acute Kidney Injury Consortium coordination? How will the plan for study management (the administrative, supervisory, and collaborative arrangements for achieving the goals of the program, including management and distribution of funds to the PCCs for the implementation and conduct of protocols, ability to assist PCCs confronting problems recruiting participants and managing data collection, etc.) and cooperation with the PCCs and the NIDDK enhance the likelihood of successfully completing the studies?

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)? Does the aggregate expertise across the proposed Natural History of Acute Kidney Injury Consortium provide the comprehensive knowledge and capability needed for appropriately conceptualizing and addressing the substantive and methodological issues underlying acute kidney injury?

What is the expertise, training, and experience of the PI in planning and conducting clinical studies? Do the PIs have adequate administrative capabilities? Is the time the PIs plan to devote to the program for the effective conduct of clinical studies adequate?

Do the investigators state their willingness to participate in joint meetings, share methods and data resources, and embark on collaborative efforts to decide the overall research directions? What is the investigator’s stated willingness and ability to work with other Network components (PCCs, the DCC and the NIDDK [(and participating NIH ICs and offices)]?

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? Does the applicant institution have a history of, and current commitment to, collaborative research? How adequate are the institutional assurances to provide resources and/or support related to fiscal administration, personnel management and equipment? What kind of dedicated space will be provided?

2.A. Additional Review Criteria:

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

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

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

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

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 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 expects that grant 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/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 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

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

2.A.1. Principal Investigator Rights and Responsibilities

PCC: The Principal Investigator at each PCC will have the primary responsibility of proposing protocols, estimating the costs of protocols, participating in their overall development and implementation, conducting the protocols, recruiting and enrolling subjects into approved protocols, assuring quality of participant management and protocol adherence, collecting and transmitting data to the DCC in a timely manner, analyzing and publishing the data. All individual PCCs must agree to participate in a cooperative and interactive manner with one another, with the DCC and with the NIDDK (and participating NIH ICs and offices) in all aspects of the Natural History of Acute Kidney Injury Consortium. PCC PIs will accept awards from the DCC for the support of SC and SAC approved research protocols based on per-participant (capitated) rates and actual numbers of participants enrolled, followed, and completing the study. Each Clinical Center will be subject to annual administrative review.

The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archival and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The DCC will work with the NIDDK Biosamples Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. In addition, the DCC will coordinate with the NIDDK repository to prepare the collected data for eventual archiving and distribution. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the Natural History of Acute Kidney Injury Consortium SC will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time.

DCC: The Principal Investigators will have the primary responsibility for working with other Natural History of Acute Kidney Injury Consortium investigators in all aspects of the study protocols and procedures, including any modification of study design, conduct of the study, data collection, quality control and study adherence, data analysis and interpretation, preparation of publications, and relevant reports for the steering committee, the NIDDK-appointed external advisory committee (s), appropriate regulatory or safety authorities, and the NIDDK. The PI is expected to work cooperatively with PCCs and oversee the implementation of and adherence to common protocols, as well as assure quality control of the data collected and its subsequent analysis. The DCC will schedule, organize and perform clinical site visits as required, during the conduct of the clinical trials. In addition to scheduling, organizing (including developing the agenda with the Natural History of Acute Kidney Injury Consortium investigators) and attending regular meetings and monthly telephone conferences, the DCC will be expected to maintain close communications with the NIDDK Project Scientist and the PIs of the Clinical Centers. The DCC will perform analyses as outlined in the Natural History of Acute Kidney Injury Consortium protocols, and as suggested by the members of the Natural History of Acute Kidney Injury Consortium SC, as well as propose original analyses to the collaborative group for their consideration. The DCC will prepare periodic reports on recruitment, quality control, study adherence, patient safety, and final results to the Steering committee, the NIDDK and the NIDDK-appointed external advisory committee (s).

The DCC will establish, maintain and provide appropriate oversight to subcontracts for Central Laboratories and other necessary adjuncts to the study, as necessitated in the study protocols. For all Central Laboratories collected for the Natural History of Acute Kidney Injury Consortium, the DCC will coordinate coding, shipping, and receipt in collaboration with study sites, and regularly monitor data quality control from the Central Laboratories.

The Principal Investigator responsibilities regarding Natural History of Acute Kidney Injury Consortium SC membership 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

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

The NIDDK will appoint a Program Officer, who apart from the Project Scientist, will be responsible for normal program stewardship of the award, monitoring of patient recruitment and study progress, and ensuring disclosure of conflicts of interest, and adherence to NIDDK policies. Specifically the Program Officer will:

2.A.3. Collaborative Responsibilities

The management of the Clinical Research of Acute Kidney Injury Consortium includes committees with the following functions:

Steering Committee (SC)

Awardee(s) agree to the governance of the study through a SC. The SC will consist of the PCC PIs (one from each PCC), the PI of the DCC, and the NIDDK Project Scientist. The SC will be the main governing body of the Natural History of Acute Kidney Injury Consortium and will have primary responsibility for developing research protocols by consensus, supervising the conduct of the studies, and reporting results. The SC will ensure that studies are properly conducted and monitored, that data are appropriately analyzed and interpreted, and that study results are reported in the scientific literature in a timely manner. The SC will develop and ensure compliance with Natural History of Acute Kidney Injury Consortium policies and procedures, identify and prioritize topics for investigation, evaluate protocols proposed by the PCCs, and develop consensus protocols for submission to the SAC for approval. Each member of the SC will have one vote. The SC may meet in person as often as three to four times in the first 12 months of the study, and two to three times per year thereafter. All major scientific decisions will be determined by majority vote of the SC. Subcommittees of the SC will be established as necessary, and will include, at a minimum, a Publications and Presentations Subcommittee, a Research Subcommittee, a Safety Committee and a Quality Control Subcommittee. In-person meetings of the SC will ordinarily be held in the Bethesda MD/ metropolitan Washington DC area.

An outside chairperson, who is not participating as an investigator, may be selected by the NIDDK to serve on the SC; alternatively, the chairperson position may be held by one of the PIs by consensus of the SC. The Study Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations. The Study Chair will plan network activities, oversee network functions, conduct SC meetings, and cast tie-breaking votes in that committee.

Scientific Advisory Committee (SAC)

A SAC will have responsibility for overall monitoring of the safety of ongoing Natural History of Acute Kidney Injury Consortium studies and will advise the NIDDK and the SC on their conduct. The SAC will develop stopping rules as necessary for each protocol. When appropriate, the SAC will review interim data analyses regarding the potential need to terminate studies, and make recommendations to the Director of the NIDDK and the SC. In addition, the SAC will evaluate planned Natural History of Acute Kidney Injury Consortium protocols, with an emphasis on participant safety, and with additional ad hoc scientific and/or clinical experts as needed. Members of the SAC will be appointed by the Director, NIDDK who will be provided a list of nominees identified by the SC. Each member of the SAC will have one vote. The PI of the DCC and the NIDDK Project Scientist will attend open sessions of SAC meetings as non-voting members. Meetings of the SAC will ordinarily be held in the Bethesda MD/ metropolitan Washington DC area. Because the Board serves as an independent group advisory to the NIDDK, study investigators will not communicate with Board members regarding study issues. All study protocols performed by the Consortium must be approved by the SAC and approved by the NIDDK before initiation.

Additional Provisions

The NIDDK reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control, (c) major breach of the protocol or substantive changes in the agreed-upon protocol with which NIDDK cannot concur, (d) attainment of a major study endpoint before schedule with persuasive statistical significance, or (e) human subject ethical issues that may warrant a premature termination.

Upon completion of the project, awardees are expected to put their 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, for the conduct of research at no charge other than the costs of reproduction and distribution.

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.

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:

Paul Eggers, Ph.D.
Division of Kidney, Urologic and Hematologic Disease
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 615
Bethesda, MD 20892-5458
Telephone: (301) 594-7717
FAX: (301) 480-4273
Email: pe39h@nih.gov

Christine Maric, Ph.D.
Division of Kidney, Urologic and Hematologic Disease
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 630
Bethesda, MD 20892-5458
Telephone: (301) 594-7712
FAX: (301) 480-4273
Email: cm630d@nih.gov

2. Peer Review Contacts:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd.
Room 752, MSC 5452
Bethesda, MD 20892-5452
Telephone: (301) 594-8885
FAX: (301) 480-3505
Email: fc15y@nih.gov

3. Financial or Grants Management Contacts:

Charlette Kenley
Grants Management Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 723
Bethesda, Maryland 20892-5456
Telephone: (301) 594-8847
FAX: (301) 594-9523
E-mail: ck128k@nih.gov

Section VIII. Other Information

Required Federal Citations

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.

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://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/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. 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 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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