Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title

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

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA-DK-07-501

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-DK-12-507

Companion Funding Opportunity

Not Applicable

Number of Applications

Only one application per institution as defined in  Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847; 93.837; 93.865

Funding Opportunity Purpose

The NIDDK invites Cooperative Agreement applications for a limited competition from the  two Clinical Coordinating Centers (CCC), the Data Coordinating Center (DCC) and the Central Biochemistry Laboratory (CBL) already involved in The Chronic Kidney Disease in Children (CKiD) consortium.  The Clinical Centers will continue to evaluate enrolled subjects, recruit new subjects, and continue to work together cooperatively with the existing DCC and CBL of the study as a Consortium. Participant evaluations in some domains will be expanded, and follow-up will extend beyond the onset of End Stage Renal Disease (ESRD). 

Key Dates
Posted Date

August 31, 2012

Open Date (Earliest Submission Date)

October 12, 2012

Letter of Intent Due Date

October 12, 2012

Application Due Date(s)

November 14, 2012, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2013

Advisory Council Review

May 2013

Earliest Start Date(s)

July 2013

Expiration Date

November 15, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

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 Biochemistry 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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) invites applications for this limited competition FOA from eligible applicants. 

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 

In response to a competitive FOA issued in 2002, and a limited competition FOA issued in 2007, awards to CKiD investigators were approved and awarded. CKiD is a consortium composed of two clinical coordinating centers, a Data Coordinating Center, and a Central Biochemistry Laboratory.

The original FOA called for creation of a Consortium of collaborating investigators to recruit a cohort of 540 children with mild to moderate chronic kidney disease (CKD), and to follow these children in a prospective fashion 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 data and biosamples obtained would be available to the broader scientific community for retrospective analyses.

Prior to this endeavor there had been no large-scale prospective studies of pediatric chronic kidney disease. CKiD has succeeded in establishing a collaborative, multi-disciplinary consortium composed of pediatric nephrologists, cardiologists, psychologists, and epidemiologists. The consortium completed the targeted enrollment by November 2007 and has collected data in the major domains described in the goals of the original FOA. The data collected has revealed novel information about the cohort of children being studied and 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 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, including several ancillary studies and collaboration with the European ESCAPE trial.

In January 2012, the NIDDK convened a meeting of an expert panel to review both CKiD and the NIDDK-sponsored CRIC study, after having a scientific meeting highlighting the findings from the two studies. Based on study findings to date, and observations of the expert panel, the NIDDK would like to continue the CKiD study for an additional five years, with some modification of the current protocol.

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 include:

(1) to continue to encourage novel approaches to identification of risk factors for CKD progression, including further work on some of the preliminary environmental exposure findings,  and continuing the ongoing genetic analyses

(2) to increase the recruitment of both minority participants and participants with glomerular disease into the cohort

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

(4) to expand the cardiovascular evaluation of the cohort, and intensify this as participants near ESRD

(5) to recruit study participants early in the course of CKD and consider expanding the eGFR formula development to include patients with a higher GFR.

(6) to continue to analyze the substantial amount of data already collected.

(7) to provide a broad data resource to the scientific community for further advancing chronic kidney disease research.

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 applications 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 data to the DCC and Central Biochemistry Laboratory.  The CCCs 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 expected to share data and patient specimens with investigators outside the Consortium, consistent with achieving the goals of the program, under policies and procedures to be determined by the NIDDK together with the Steering Committee and the Observational Study Monitoring Board.

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 Observational Study Monitoring 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 (CBL)

The CBL 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 CBL 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 CBL.

4. Steering Committee

A Steering Committee composed of the program director(s)/principal investigator(s) (PDs/PIs) of the CCCs, the DCC, the CBL, and the NIDDK Project Scientist will be the main governing body of the study. A representative from the NHLBI will also participate at all steering committee meetings for input regarding research interests and topics specific to that institute.  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. Observational Study Monitoring Board

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

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

Renewal
The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NIDDK intends to commit $3.2 million, and NHLBI intends to commit $250,000 and NICHD intends to commit $200, 000 in FY2013 to fund four awards.

Award Budget

An applicant may request a budget for direct costs up to $500,000-$700,000 for the Clinical Coordinating Centers, $800,000 for the Data Coordinating Center and $200,000-$215,000 for the Central Laboratory per year.

Award Project Period

The project period will be 5 years. 

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

Individuals from the existing CKiD CCCs, DCC or CBL 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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

The letter of intent should be sent to:

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide must be followed, with the following exception:

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Not Applicable

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

4. Intergovernmental Review (E.O. 12372)

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.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.   

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIDDK, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? What progress has been made during the previous funding period in developing appropriate infrastructure and meeting study goals? Have ancillary studies been encouraged to allow access of the study data to a wider audience?  

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Have the investigators participated in key activities in the prior project periods, including membership on subcommittees of the Steering Committee?  Is there a commitment to participate in the analyses and publication of findings?  Is there clear commitment to conduct and continue the CKiD study?   

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

Clinical Coordinating 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 two phases of the CKiD Study?  Have measures of quality of data been included in the application from the prior phases of the cohort study?   Has the implementation of the phase II study protocol in all currently enrolled study participants and the transition to phase III been clearly described?  Has the applicant provided an estimate of the number of participants recruited in Phase I/II 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 two phases of the CKiD Study?  Has the quality of data collected, rates of follow-up, and performance of procedures from prior phases been adequately described?  Has the applicant proposed a plan for data quality control for phase III?  Has the applicant described a proposed leadership role of the Data Coordinating Center in phase III?  Are analysis plans described for data collected in the prior project periods as well as for the next five year period? Have 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?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  Is there evidence of institutional support? Has the organizational and administrative structure of the Clinical Coordinating Center been clearly described?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.   

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.   

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council.  The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.      

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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

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

The PD(s)/PI(s) will have the primary responsibility for:

1. Developing the research design and study protocol, including definition of objectives and approaches, sample size and power calculations, and establishing procedures for participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and publication of results.

2. Establishing a Steering Committee to implement, coordinate and manage the project(s). Awardee(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees will be required to accept and implement the common protocol(s) and procedures approved by the Steering Committee.

3. Designating Protocol Chairs. The Principal Investigators (for studies involving multiple coordinated awards) shall designate a single Protocol Chairperson (if the Principal Investigator does not assume this role) for each protocol to be carried out by the study group. The Protocol Chairperson shall function as the scientific coordinator for the protocol and shall assume responsibility for obtaining approval to implement the protocol from the Steering Committee and for developing and monitoring the protocol. Significant modifications to approved protocols must be approved by the Steering Committee.

4. Implementing collection of data specified by the study protocol, by the Steering Committee. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.

5. Establishing procedures for data quality and completeness. Awardees are responsible for ensuring accurate and timely assessment of the progress of each study, including development of procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) for clinical trials, as simple as appropriate in order to facilitate cooperation/referral of study participants by physicians to avoid unnecessary expense; and (3) sufficiently staffed across the participating institutions. For research involving multiple awards, a plan for analysis of pooled data will be developed by the Steering Committee.

6. Submitting interim progress reports, when requested, to the NIDDK Program Director including as a minimum, summary data on protocol performance. For coordinated multiple awards or a multi-site single award, the NIDDK Program Director may require additional information from individual awardees/sites. Such reports are in addition to the required annual noncompeting continuation progress report.

7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.

8. Reporting of the study findings. The awardee(s) will retain custody of and have primary rights to the data developed under these awards, subject to the Government rights of access consistent with current HHS, PHS and NIH policies. The awardee must also be adherent to Study Publication and Presentation Policy.  The NIDDK will have access to and may periodically review all data generated under an award. NIDDK staff may co-author publications of findings with awardees consistent with NIH and study policies.

9. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIDDK support; or special access to study results, primary data/summary information, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIDDK.

10.  Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and steering committee policies on publications.

11.  Maintaining confidentiality of information:  The awardee(s) will maintain the confidentiality of the information developed by the investigators (i.e., protocols, data analysis, conclusions, etc.) as well as proprietary information of a company collaborating with the study.

12. 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 PD/PI or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution. In addition, if applicable, the PD/PI or his/her designee will work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data will be available to the wider scientific community in accordance with the NIH policy on Data Sharing   (http://grants.nih.gov/grants/policy/data_sharing/ and, http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

13. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If applicable, the PD/PI or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html.

NIDDK staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

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

1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

2. For multi-center studies, participation in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serving as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:

a. Assisting by providing advice in the management and technical performance of the investigations, coordinating required regulatory clearances for investigational agents used in the study, which are held by NIDDK. The NIDDK may reserve the right to cross file or independently file an Investigational New Drug Application or an Investigational Device Exemption form with the FDA.

b. The NDDK Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.

c. Reviewing procedures for assessing data quality and study performance monitoring.

d. The NIDDK Project Scientist or designee may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participate in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.  

In addition, a separate NIDDK Program Official identified in the Notice of Grant Award will be responsible for the normal stewardship and monitoring of the award including review and approval of all progress reports and all budgetary decisions.  Additional responsibilities include. 

Interacting with the principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.

Reviewing and approving protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.

The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; and (f) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.

Making recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.

Appointment of a Data and Safety Monitoring Board (DSMB) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.

Areas of Joint Responsibility include:

In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:

1. Steering Committee.

A Steering Committee organized by the study investigator(s) will be the main governing body of the study.

The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of  results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.

The Steering Committee will be composed of all Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.

A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK (see item D2 below) and by interacting closely with the awardees during protocol development and implementation.

2. External Study Oversight

An independent Data and Safety Monitoring Board will be established by the NIDDK for Phase III clinical trials or other high risk studies as appropriate. The Data and Safety Monitoring Board will review interim results periodically and provide guidance to the NIDDK.

Dispute Resolution:

Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIDDK may be brought to Dispute Resolution.  A Dispute Resolution panel will be composed of three members --one selected by the awardee (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIDDK, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Marva Moxey-Mims, M.D.
Director Pediatric Nephrology & Renal Centers Programs
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone:  (301) 594-7717
Email: mm726k@nih.gov

Kristin Burns, M.D.
Heart Development and Structural Diseases Branch
National Heart, Lung and Blood Institute
Telephone: (301) 594-6859
Email: Kristin.Burns@nih.gov

Lynne Haverkos, M.D., M.P.H.
Child Development and Behavior Branch
National Institute of Child Health and Human Development
Telephone:  (301) 435-6881
Email: lh79r@nih.gov

Peer Review Contact(s)

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-8897
Email: fc15y@nih.gov

Financial/Grants Management Contact(s)

Pamela Love
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 435-6198
Email: pl48m@nih.gov

Shelia Ortiz
National Heart, Lung and Blood Institute
Telephone: (301) 435-0166
Email: so60r@nih.gov

Bryan S. Clark, M.B.A.
Chief Grants Management Officer
Eunice Kennedy Shriver National Institute   of Child Health and Human Development
Telephone: (301) 435-6975
Email: clarkb1@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

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 Part 52 and 45 CFR Parts 74 and 92.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH . . . Turning Discovery Into Health

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.