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://www.niddk.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov)
National Institute of Child Health and Human Development (NICHD),  (http://www.nichd.nih.gov) 

Title: NIDDK Limited Competition for Continuation of the Prospective Study of Chronic Kidney Disease in Children (U01)

Announcement Type
This is a reissue of RFA-DK-03-012 which was previously released November 26, 2002

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

Request For Applications (RFA) Number: RFA-DK-07-501

Catalog of Federal Domestic Assistance Number(s)
93.849, 93.837, 93.865

Key Dates
Release Date:  October 5, 2007
Letters of Intent Receipt Date: November 14, 2007
Application Receipt Date December 11, 2007
Peer Review Date(s): February-March 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 2008
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: December 12, 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

The purpose of this funding opportunity announcement (FOA) is to continue the support for the Clinical  Coordinating Centers, Data Coordinating Center and Central Laboratory  that have been involved in The Chronic Kidney Disease in Children (CKiD) consortium. The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in collaboration with the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Child Health and Human Development (NICHD) invites applications for this limited competition Request for Applications (RFA) from eligible applicants.  The program will fund, up to a maximum of 5 years, four U01 cooperative agreement awards to continue the prospective epidemiological study of children with chronic kidney disease.

The investigators will continue to collect study data according to the CKiD Protocol; collect and transmit biologic, genetic and other samples and familial and clinical data as delineated in the Protocol and Manual of Operations.  The primary goals of this study remain as delineated in the original FOA: to determine the risk factors for decline in renal function; the incidence of, and risk factors for, impaired neurocognitive development and function; the prevalence of risk factors for cardiovascular disease; and the long-term effects of growth failure and its treatment.

Background 

The incidence of end-stage renal disease (ESRD) in patients age 0 – 19 years in the United States is 14 per million population, according to the 2006 USRDS Annual Data Report. The primary etiologies vary with age, but structural anomalies predominate. Data in the most recent report from the Chronic Renal Insufficiency arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) indicate about two thirds of the patients on the registry had some type of structural anomaly. Numerous metabolic derangements occur in chronic kidney disease (CKD) and significantly impact on the overall well-being of affected children. Of the negative effects of pediatric renal disease, growth impairment is the best documented and studied, but there is very little systematic information about the magnitude of other developmental problems. In fact, prior to this endeavor there had been no large-scale prospective studies of pediatric chronic kidney disease.

In response to a competitive RFA issued in 2002, awards to CKiD investigators were approved in September 2003 and awarded in October, 2003. CKiD is a consortium composed of two clinical coordinating centers  U01s (U01 DK066174, Susan Furth, Johns Hopkins University; U01 DK066143,  Bradley Warady, Children’s Mercy Hospital, Kansas City, MO) and a Data Coordinating Center (U01 DK066116, Alvaro Munoz, Johns Hopkins University).

The original RFA called for creation of Consortium of collaborating investigators to recruit a cohort of 540 children with mild to moderately impaired kidney function and to follow these children in a prospective fashion for five years in order to define factors that impact on their well-being. They were to follow a common protocol to allow for a coordinated, multi-disciplinary approach to: determine risk factors for accelerated decline in renal function; determine the incidence of, and risk factors for, impaired neurocognitive development and function; determine the nature and magnitude of neurocognitive impairment in pediatric CKD; establish brain structure/function correlates of neurocognitive impairment in pediatric CKD; examine genetic contributions to disease; determine the implications of growth failure and its treatment on morbidity and mortality; determine the prevalence of risk factors for cardiovascular disease. It also specified creation of a central repository of data and biologic samples for subsequent hypothesis based research. It was envisioned that the information obtained from this prospective cohort study of chronic kidney disease would establish natural history and outcome measures for future intervention/prevention trials. It was also envisioned that the reposited data and biosamples would be available to the broader scientific community for retrospective analyses.

CKiD has succeeded in establishing a collaborative, multi-disciplinary consortium composed of pediatric nephrologists, cardiologists, psychologists, and epidemiologists. They are on track to complete the targeted enrollment by November 2007 and have collected data in the major domains described in the  goals of the original FOA. The data collected has already revealed novel information about the cohort of children being studied and will inform the goals of this limited competition.

The Consortium developed a compelling multi-disciplinary, multi-institutional, clinical research protocol that provides pertinence, validity, reliability, and generalizability to an extent not possible with single-institutional or previous studies of pediatric CKD patients.  The Consortium has also demonstrated success in meeting challenging recruitment and retention goals and the special challenges of this complex study. The Consortium has established a broad and effective collaborative base of ongoing relationships providing expanded sources of relevant idea.

Objectives and Scope

The overall objective of this solicitation is to invite the CKiD investigators to extend the follow-up of the subjects recruited and expand on some aspects of the evaluations. The specific goals of the CKiD consortium are

(1) to encourage novel approaches to identification of risk factors for CKD progression

(2) to increase the recruitment of more minority subjects into the cohort

(3) to expand on the prenatal and neonatal history of subjects in the cohort, based on the data gathered so far

(4) to expand the cardiovascular evaluation of the cohort

(5) to conduct in depth neuroimaging studies on a subcohort of the study subjects.

Study Design

The individual CCCs, the DCC and Central Laboratory participating in the cooperative study have jointly developed the standardized protocol.

The Consortium will jointly analyze data from its study populations. The consortium has developed a mechanism to solicit ancillary research proposals from investigators who have enrolled patients in the CKiD study.  CKiD is collecting  specimens that include sufficient material for measurements to be made based on hypotheses developed by the Steering Committee and also for storage of sufficient specimens that material will be available in the future when new technology or approaches may be applied to hypothesis testing.

Study Components

1.  Clinical Coordinating Centers (CCCs)

Up to two awards will be made for CCCs that are responsible for the recruitment, evaluation and the long-term follow-up of study subjects. 

CCCs will continue to submit data and/or samples as required by the protocol for testing or storage, samples for a DNA and/or cell line repository, as well as familial data to the DCC and Central Laboratory.  The CCC must work in concert with the DCC to continue procedures for uniform data collection, handling and transmittal of data, as well as data audits and other data quality control procedures, as has been established by the study protocol.

The Consortium will conduct analyses and will have exclusive access to data from its study population for a period of time, in accordance to a timetable determined by the CKiD Steering Committee in concordance with NIDDK. The Consortium will then be required to share data and patient specimens with investigators outside the Consortium under policies and procedures to be determined by the NIDDK together with the Steering Committee and the External Advisory Committee.

2. Data Coordinating Center (DCC)

This center will be responsible for the collection, management and analysis of the laboratory and clinical data, and coordinating communication and research with the Clinical Centers. In addition, the DCC will continue the data acquisition and transfer and continue to utilize procedures for ensuring subject  confidentiality, procedures for quality control, training, and certification, update the manual of operations, and supervise the orderly collection and transmission of data. The DCC will continue to oversee implementation and adherence to the study protocols, and assure quality control of the data collected. 

The DCC will continue to coordinate movement of biologic specimens from the participating sites to central laboratories for analysis and to the repository where samples will be stored for future analyses.  The DCC will continue to maintain the system for identification of samples and linkage of samples to a central clinical database.  In addition the DCC will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution.

The DCC will provide appropriate biostatistical, data management, and coordination and analytic expertise for the primary study, and ancillary study proposals as needed.  The DCC will continue to generate appropriately detailed reports to the Steering Committee and to the External Advisory Board at regular intervals, and will be responsible for the logistics and planning of the meetings of the Steering committee and its subcommittees.

3. Central Biochemistry Laboratory

The Central Biochemistry  Laboratory will be responsible for providing participating sites with the reagents and protocol needed for the iohexol glomerular filtration rate (GFR) measurements.  The plasma samples collected during the iohexol GFR measurements will be sent to the Central laboratory for analysis and results will be sent to the DCC. In addition, all central chemistry measurements dictated by the study protocol will be performed at the Central Laboratory.

4. Steering Committee

A Steering Committee composed of the principal investigators of the Clinical Coordinating Centers and the Data Coordinating Center and the NIDDK Project Scientist will be the main governing body of the study. A representative from both NHLBI and NICHD will also participate at all steering committee meetings for input regarding research interests and topics specific to these participating Institutes.  The Steering Committee will have primary responsibility for the general organization of the study, finalizing common protocols, facilitating the conduct and monitoring of the studies, and reporting study results.

5. Project Scientist

The NIDDK Project Scientist, will continue to assist the Steering Committee in carrying out the proposed studies (described in detail under Terms and Conditions).  The Project Scientist will provide scientific support to awardees activities, including quality control, interim data monitoring, final data analysis and interpretation, preparation of publications, and overall performance monitoring.

6. External Advisory Committee

An independent External Advisory Committee (EAC) was established by the NIDDK, NHLBI and NICHD including experts in areas such as pediatric nephrology, pediatric neurology, pediatric neuropsychology, pediatric cardiology, biostatistics, epidemiology and ethics, who are not otherwise involved in the study.  The EAC will continue to monitor protocol performance and participant safety at least annually.

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

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the NIH cooperative clinical research (U01) award mechanism..

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

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 U01is 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".

2. Funds Available

The participating IC(s), NIDDK, NHLBI and NICHD, intend to commit approximately 3.35 million dollars in FY 2008 to fund four competing continuation grants in response to this RFA. An applicant may request a project period of up to five years and a budget for direct costs up to $500,000-$700,000 for the Clinical Coordinating Centers, $800,000 for the Data Coordinating Center and $150,000-$175,000 for the Central Laboratory per year.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

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

As this FOA is a limited competition opportunity that involves a continuation of the cooperative agreements supporting the CKiD study, only the current U01 CKiD awardees and Central Biochemistry Laboratory are eligible to submit applications.

1.B. Eligible Individuals
Individuals from the existing CKiD CCCs, DCC or Central Biochemistry Laboratory with the skills, knowledge, and resources necessary to carry out the proposed research are 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 Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

None

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a 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.

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 14, 2007
Application Receipt Date: December 11, 2007
Peer Review Date(s): February-March 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 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, Digestive, and Kidney Diseases
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, Maryland 20892-5452
Bethesda, Maryland 20827 (for courier service)
Telephone: (301) 594-8897
Fax:   (301) 480-3505
Email:  fc15y@nih.gov


3.B. Sending an Application to the NIH

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

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

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

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

Francisco O. Calvo, Ph.D.
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 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 http://grants.nih.gov/grants/policy/policy.htm.

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

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

Not applicable.

Plan for Sharing Research Data

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

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

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

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/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

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

Section V. Application Review Information


1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

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

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

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

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?   What progress has been made during the previous funding period in developing appropriate infrastructure and meeting study goals?

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? Clinical Centers: Have the Clinical Center applicants described the overall rate of retention, both in terms of clinic visit, data collection, and performance of procedures, at their centers during the first phase of the CKiD Study?  Have measures of quality of data been included in the application from the first phase of the cohort study?   Has the implementation of the phase I study protocol in all currently enrolled study participants and the transition to phase II been clearly described?  Has the applicant provided an estimate of the number of participants recruited in Phase I who would be willing to participate for an additional five years? Has the applicant provided detailed plans on how high rates of follow-up will be maintained over the course of five years in phase II of the study?  Has the applicant described the process for ensuring high quality and complete data collection?  Is there clear integration of satellite site(s) into the operations of the lead Clinical Centers?  Data Coordinating Center: Has the applicant provided a comprehensive description of the clinical and demographic characteristics of the population recruited in the first phase of the CRIC Study?  Has the quality of data collected, rates of follow-up, and performance of procedures from phase I been adequately described?  Has the applicant proposed a plan for data quality control for phase II?  Has the applicant described a proposed leadership role of the Data Coordinating Center in phase II?  Are analysis plans described for data collected in the first project period as well as for the next five year period? Has the organizational plan and procedures for publications (including data analysis to support manuscripts) been clearly described? Is there a plan for support of development of ancillary study applications and analysis of data generated from ancillary studies when needed? Is there a description of the efforts necessary to coordinate the study across the participating Clinical Centers?  Is there a clear and comprehensive description of how the integrity of the data will be maintained during transmission from the Clinical Centers and during storage at the Data Coordinating Center?  Have the procedures for receipt, processing, and safe storage of biologic samples been described adequately? Central Biochemistry Laboratory: Has the applicant provided a clear description of the process for supplying all participating sites with the reagents, protocol and support needed for the iohexol glomerular filtration rate (GFR) measurements? Has the applicant given details for ensuring appropriate transmission of plasma samples collected during the iohexol GFR measurements from the participating sites to the central laboratory for analysis? Has the applicant described the data quality assurance methods for analyzing the plasma specimens and subsequent transmittal of the results to the DCC? Has the applicant described the analyses and data quality assurance methods for all central chemistry measurements dictated by the study protocol? 

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

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?  Have the investigators participated in key activities in the first project period, including membership on subcommittees of the Steering Committee?  Is there a commitment to participate in the analysis and publication of findings?  Is there clear commitment to conduct and continue the CKiD study?

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? Has the organizational and administrative structure of the Clinical Center been clearly described?  

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/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

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

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

3. Anticipated Announcement and Award Dates

Not applicable.

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the 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/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

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

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: the conduct of the study.  This will include any changes in study protocol that need to be done, coordination of IRB clearances, oversight of all sub-contracts, quality control, recruitment of study subjects, analysis of study results and close-out activities.  

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 Project Scientist will assist the Principal Investigators through the Steering  Committee in carrying out the study.  The Project Scientist will have substantial scientific-programmatic involvement in assisting in protocol refinement, quality control, interim data analysis, final data analysis and interpretation, preparation of publications, and will provide assistance in coordination and performance monitoring.  The NIDDK Project Scientist will also serve as a member of the Steering Committee.

Additionally, an NIDDK Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

The Steering Committee, composed of the Principal Investigators of the Clinical Centers, and the principal investigator of the Data Coordinating Center, the Chairperson of the Steering Committee, experts in the fields of pediatric neurology, endocrinology and cardiology and the NIDDK Project Scientist, will be the main governing board of the study.  This committee will have the primary responsibility for making any necessary changes to the study protocol, facilitating the conduct of participant follow-up and testing, monitoring completeness of data collection adherence to the protocol, timely transmission of the data to the DCC, and reporting the study results. It will also be responsible for establishing study policies in such areas as access to patient data and specimens, ancillary studies, publications and presentations, and performance standards. Each member of the Steering Committee will have one vote (NIDDK will have one vote), and all major scientific decisions will be determined by a majority vote of 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 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:

Marva M. Moxey-Mims, M.D.
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard
Room 639, MSC 5458
Bethesda, Maryland 20892-5458 (for express or courier service use 20817)
Telephone:  (301) 594-7717
FAX:  (301) 480-3510
Email:  mm726k@nih.gov

Lynne Haverkos, M.D., M.P.H.
Child Development and Behavior Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard
Room 4B05, MSC 7510
Bethesda, MD 20892-7510
Telephone:  (301) 435-6881
FAX:  (301) 480-0230
Email:  lh79r@nih.gov

Gail Pearson, M.D.
Heart Development and Structural Diseases Section
Division of Cardiovascular Diseases
National Heart, Lung and Blood Institute
6701 Rockledge DriveRoom 8104, MSC 7940
Bethesda, MD 20892-7940
Telephone: (301) 435-0510
Fax: (301) 480-1454
Email: gp62n@nih.gov

2. Peer Review Contacts:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes, Digestive, and Kidney Diseases
6707 Democracy Boulevard
Room 752, MSC 5452
Bethesda, Maryland 20892-5452
Bethesda, Maryland 20827 (for courier service)
Telephone: (301) 594-8897
Fax:   (301) 480-3505
Email:  fc15y@nih.gov

3. Financial or Grants Management Contacts:

Carolyn Kofa
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 727
Bethesda, MD 20892-5456
Telephone: (301) 594-7687
Fax: (301) 480-3504
Email: ck104i@nih.gov 

Bryan S. Clark, M.B.A.
Chief Grants Management Officer
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Blvd, MSC 7510
Rockville, MD 20892-7510
Telephone: (301) 435-6975
Fax: (301) 402-0915
Email: bc208o@nih.gov

Anthony Agresti
Team Leader
Office of Grants Management
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7158
Bethesda, MD 20892
Telephone: 301-435-0186
Fax: 301-451-5462
Email: ta32q@nih.gov


Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

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

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

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.

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

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

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://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 RFA 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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