It is critical that applicants follow the Research (R) Instructions in the SF424 (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.

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

Purpose

This FOA requests a single application from the grantee currently serving as the Scientific and Data Coordinating Center (SDCC) for the Chronic Renal Insufficiency Cohort (CRIC) Study to continue to serve in that capacity. The Scientific and Data Coordinating Center is required to have an infrastructure of personnel and effective procedures to continue to collect data from the Clinical Centers, perform quality control, and store and manage the data for analysis. They will, in conjunction with CRIC Clinical Center investigators, conduct analyses for scientific manuscripts to be published in the peer-reviewed literature. They will also coordinate the collection of biological samples from the Clinical Centers, receive and store the samples, and maintain them under appropriate conditions and preserve sample identity for their eventual archiving at the NIDDK Repository. This FOA will support the SDCC to provide leadership in nephrology, clinical research study design, biostatistics, bioinformatics, project management, and other key areas in support of protocol development, implementation, and analysis. While the primary objective of this FOA is to further study the long-term courses and consequences of chronic kidney disease (CKD), the scope of the CRIC Study will be expanded and modified substantially by:

1) Implementing novel remote data capture technologies in sub-groups of study participants to examine sub-clinical acute declines in kidney function and identify cardiovascular phenotypes;

2) Utilizing state-of-the-art statistical and bioinformatic methods to analyze the collected data, integrating multiple domains of information to identify clinically important sub-groups of patients, furthering our understanding of CKD;

3) Disseminating results of these analyses through the publication of integrative manuscripts;

4) Engaging a broader set of investigators external to the immediate study group to provide opportunities to analyze the data and participate in the parent study by means of ancillary studies;

5) Developing opportunities for local analysis of data by CRIC Study investigators and other qualified researchers at their institutions, and investigators outside the study group ("disseminated data analysis");

6) More closely aligning the goals and objectives of the CRIC Study with other NIDDK supported research studies including the recently initiated Kidney Precision Medicine Project and cooperating fully with these studies to provide access to study participants (through the usual ancillary study mechanisms), data, and biological samples;

7) Establishing and administering through the SDCC, an annual set aside of funds (an "opportunity pool") to support competitive pilot and feasibility studies to explore novel research questions and promote novel analytic approaches in response to emerging science; and;

8) Conducting active and ongoing outreach to the research community to bring in expertise not currently available to the study group to serve as "collaborating investigators".

The study will also continue to provide data and biological samples from enrolled participants to the NIDDK Repository in accordance with Institute guidelines. They will also promote and conduct ancillary studies to expand the scope of the science to be conducted in the next project period and continue to promote research career development in CKD through facilitating career development (K) and other awards that access CRIC Study participants directly or access data and/or samples from the NIDDK Repository.

Background

Chronic kidney disease is a major public health and medical problem in the United States and globally. The overall prevalence of CKD in the general U.S. population is approximately 15 percent. The economic and health impact of CKD, especially after kidney failure (end-stage renal disease) and initiation of renal replacement therapy, is substantial. Although adjusted mortality rates of patients receiving maintenance hemodialysis have decreased they remain unacceptably high; annual costs for hemodialysis treatment are about $25 billion dollars. The impact of CKD prior to kidney failure is also substantial. Patients with earlier stages of CKD experience higher overall mortality, increased burden of cardiovascular disease and related hospitalizations, other co-morbid illnesses, and excess medical costs than persons without these chronic diseases.

To advance the understanding of the courses and consequences of CKD, the NIDDK established the CRIC Study in 2001. The original aims of this multi-center, prospective, observational study were 1) to identify and evaluate the impact of novel and traditional risk factors for rapid progression of CKD and the overall course of decline in kidney function characteristic of these diseases, and 2) to study novel and traditional risk factors for cardiovascular disease within the setting of established CKD. An initial cohort of about 3,600 participants were recruited from 2003 to 2007. A second cohort of men and women who were older and on average had better kidney function (less severe disease) was recruited from 2013 to 2015. An additional 327 study participants with CKD and of Hispanic ethnicity were recruited into the study at one of the Clinical Centers through an investigator initiated (R01) ancillary study grant; those participants are followed and assessed with the parent study protocol permitting combined analyses. At the start of the next project period of this FOA, it is projected that approximately 3,150 participants (the "primary cohort") will be actively followed. The study has spawned many ancillary studies through investigator initiated (R01) grants and has fostered careers in both basic and clinical research of CKD through career development (K) awards from the National Institutes of Health as well as through other sources of funding. The study group, through the SDCC, provides both data and biological samples on a regular basis to the NIDDK Repository. The study group also actively collaborates (providing data and/or samples) with ongoing studies supported by the NIDDK, including the Chronic Kidney Disease Biomarker Consortium. The study also has an international collaboration with the International Network of CKD Studies (iNET-CKD) sponsored by the International Society of Nephrology.

Research Objectives

The overarching objective of the next project period of the CRIC Study to be supported by this FOA is to characterize the courses and consequences of CKD in substantially greater depth than heretofore achieved over the past years of follow-up of the CRIC Study participants. The longer-term goal is to provide information that will lead to more personalized care of patients with CKD, consistent with the goals of the recently launched NIDDK Kidney Precision Medicine Project. The in-depth characterization of the biological and behavioral aspects of CKD will require careful and extensive assessment of the study participants. The CRIC Scientific and Data Coordinating Center plays a central role in facilitating the conduct of studies undertaken by the CRIC Clinical Centers. The major objectives of the next five years of the study include:

1) To continue follow-up and assessment of study participants with emphasis on the treated natural history of CKD and CVD, according to approved and common study protocols;

2) To study patterns of kidney function and damage through in-home testing of serum creatinine and urine albumin in a sub-set of participants and to relate these patterns to CKD progression and cardiovascular disease incidence, hospitalization, and other outcomes of clinical and patient interest;

3) To advance the understanding of selected cardiovascular diseases, including heart failure, the most common CVD observed in the CRIC Study cohort, and atrial and ventricular dysrhythmias by identifying cardiovascular sub-phenotypes through ambulatory monitoring of cardiovascular health in a sub-set of participants;

4) To utilize state-of-the-art methods in biostatistics and bioinformatics promulgated by the SDCC, biostatisticians and bioinformaticians affiliated with the CRIC Clinical Centers as engaged non-paid (from this FOA) collaborators, and those outside the study group, to analyze complex, longitudinal datasets. Such methods should incorporate into the analyses a multitude of exposure and outcome variables;

5) To fully integrate the previously collected data and information planned to be collected during the next project period under this FOA through robust analyses that will result in "integrated", high-impact papers published in high quality journals and reports that take advantage of the longitudinal nature (repeated measures) of the data. This includes analyses incorporating data generated by other study groups using CRIC data and/or samples (e.g., the NIDDK CKD Biomarker Consortium, R01 supported and other ancillary studies);

6) To foster and conduct ancillary studies supported by funding outside this FOA;

7) To promote data analysis by CRIC Clinical Center investigators and their affiliated investigators to extend analytic capacity of the CRIC SDCC;

8) To facilitate data analysis by qualified investigators outside the immediate study group with minimal interaction with the SDCC to extend the number and type of analyses; and

9) To promote and collaborate, when applicable, with investigators funded through the opportunity pool pilot and feasibility study program.

See Section VIII. Other Information for award authorities and regulations.

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.

Only the current CRIC SDCC awardee under RFA-DK-12-508 is eligible to apply under this limited competition FOA.

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 not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

Only the current Principal Investigators of the CRIC SDCC are eligible to apply under this FOA.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

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:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

John Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Fax: 301-480-3505
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. For this specific FOA the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

The application must include a request to support travel for members of the Observational Study Monitoring Board (OSMB). Funds should be sufficient to support one face-to-face OSMB meeting per year for eight to ten members.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Specific Aims:

The applicant is to provide the overall objective for the entire application and indicate separately specific aims to be accomplished by follow-up of the primary cohort and sub-studies of in-home testing of kidney function and damage and ambulatory measurement of cardiovascular health using non-invasive wearable remote biosensors that will be carried out by the Clinical Centers.

Research Strategy

• Describe the study design for continued follow-up of the enrolled participants, including type and frequency of measurements and CKD and CVD-related outcomes and proposed analyses.
• Describe how the SDCC will coordinate the design of the sub-study of in-home clinical testing of serum creatinine and urine albumin, including clear research questions or hypotheses to be addressed, proposed measurements to be made, and criteria for enrollment of participants. Overall sample size estimates and statistical power calculations must also be provided. Describe how those data will be analyzed as they relate to outcomes of interest.
• Describe how the SDCC will coordinate the design of the studies of ambulatory measurement of cardiovascular health using remote sensors, including clear research questions or hypotheses to be addressed, proposed measurements to be made, and planned criteria for enrollment of participants. Overall sample size estimates and statistical power calculations must also be provided. Describe how the data will be analyzed and how these measures relate to cardiovascular and other outcomes of interest.
• Describe the integration of data from the two sub-studies and how combined analyses, if planned, will be performed.
• Discuss how the SDCC will coordinate with the Clinical Centers during further follow-up of the primary cohort and sub-studies of patterns of kidney function and ambulatory measures of cardiovascular health to identify new sub-groups of patients with CKD and inform the care and management of these patients as well future clinical trials.
• Describe how state-of-the-art methods in biostatistics and bioinformatics will be applied to both existing data and information planned to be collected in the next project period to fully exploit both multiple exposure and outcome variables.
• Describe how disparate measurements will be combined and analyzed to produce integrated manuscripts that will maximize their impact on the field of adult CKD.
• Describe how investigators outside the current grantees will be brought into the study group to meaningfully supplement expertise to inform study design, data analysis and interpretation.
• Discuss how the SDCC will facilitate the promotion of ancillary studies, including those related to career development, and will facilitate their implementation consistent with study policies.
• Describe how the analytic capabilities of the study group can be expanded by providing data to investigators affiliated with CRIC Clinical Centers (but not supported by this FOA) and to other qualified investigators not directly associated with the study.
• Describe how the "opportunity pool" of funds set aside with the budget of the SDCC to support pilot and feasibility studies will be established and administered, including review and selection of awardees.
• Describe the type, frequency, and estimated amounts of biological samples to be sent to the NIDDK Repository during the next project period. Outline the process for sample collection by the Clinical Centers, local processing by the Clinical Centers, and processing and storage by the Scientific and Data Coordinating Center prior to ultimate deposition in the Repository.
• Describe the type and timing of data collected to be sent to the NIDDK Repository.
• Provide a statement of willingness by the SDCC to fully participate in the cooperative nature of the CRIC Study as outlined in Section VI, "Cooperative Agreement Terms and Conditions of Award, including how the SDCC will interact with the NIDDK appointed Observational Study Monitoring Board.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data and Resource (Biological Sample) Sharing Plan.

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.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date 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.

This initiative is not subject to intergovernmental review.

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.

Applications must be submitted electronically following the instructions described in the SF424 (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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. 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 and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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.

Reviewers will provide an overall impact 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).

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.

Does the proposed Scientific and Data Coordinating Center address the needs of the CRIC Study group? Is the scope of activities proposed for the SDCC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research to be conducted by the study group? Has a compelling justification been made to continue to follow the primary cohort and to undertake proposed sub-studies?

Have the PD(s)/PI(s) demonstrated significant prior experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Scientific and Data Coordinating Center? Does the applicant have experience overseeing selection and management of sub-awards, if needed? Are the investigators proposed to conduct statistical analyses well-versed in state-of-the-art methods for complex, longitudinal data sets? Has the applicant provided clear evidence of past accomplishments including success in coordinating the CRIC Study group? Has a detailed description included in the application on how the SDCC provides leadership to the Clinical Centers, with specific reference to investigators named in the grant application, to promote high rates of follow-up of study participants, obtaining complete and high-quality data, collection and processing of biological samples, participation in and initiating ancillary studies, organization and operation of the Steering Committee and its subcommittees and publications and presentations of the data as well as other key measures of past success?

Has the applicant described how state-of-the-art methods in biostatistics and bioinformatics, will be employed to analyze the newly collected data, including data from the sub-studies, and how these data will be integrated with existing, previously collected clinical and behavioral measures?

Has the applicant described how state-of-the-art methods in biostatistics and bioinformatics will be utilized in future analyses to generate integrated, high quality publications that include new and previously collected information?

Has the applicant described new cardiovascular sub-phenotypes and patterns of kidney function likely to be identified in the sub-studies and how these subgroups will inform the study of CKD?

Does the application describe the feasibility of longer-term follow-up of the primary cohort? Have a clear and compelling rationale and justification been made in the application to continue follow-up of previously recruited study participants (the primary cohort)? Does the application include a clear description of the design of the study, including sample size estimates and power calculations, to follow-up the primary cohort? Has the applicant described what new insights will be obtained from further follow-up of the primary cohort and how these findings might lead to improved care and management of patients with CKD and inform the design of future clinical trials?

Does the application include clear and concise descriptions of the goals and designs of the sub-study protocols, including justification of entry criteria and sample size estimates and power calculations, for in-home testing of kidney function and damage and ambulatory measures of cardiovascular health in sub-sets of the primary cohort?

Are the plans for recruitment of study participants for the two sub-studies from the primary cohort described in sufficient detail and realistic?

Has the applicant provided clear evidence from prior experience and proposed plans to assist the Clinical Centers to maintain high rates of follow-up and acceptable data quality and completeness in the future project period?

Are plans to monitor the performance of the Clinical Centers in conducting the sub-studies well described? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrae animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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?

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 score, but will not give separate scores for these items.

Data Dissemination and Analysis

Does the application include a feasible plan to implement new approaches to dissemination of data and data sharing with the broader research community to permit data analysis to extend the number and type of analyses from the CRIC Study but does not duplicate or overlap with the function of the NIDDK Repository?

Interaction with Observational Study Monitoring Board

Has the applicant provide sufficient detail on how the SDCC will interact with the Observational Study Monitoring Board including preparation of reports, presentations to the Board, and implementing their recommendations regarding study design, improvement in performance, analytic strategies, after review by NIDDK?

Opportunity Pool Administration

Does the application include an adequate plan to solicit proposals, evaluate them and administer the opportunity pool for pilot and feasibility studies?

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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

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

Not Applicable

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 score.

Not applicable.

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).

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) Genomic Data Sharing Plan (GDS).

For study groups involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 with 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 may be shared among the awardees and the NIH as defined below.

The Principal Investigators will have primary responsibility for:

1. Developing the research design and study protocols, 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 of the Steering Committee and other subcommittees, as appropriate, meeting periodically. Awardees will be required to accept and implement the common protocols and procedures approved by the Steering Committee.

3. Designating Protocol Chairs. The Principal Investigators (for studies involving multiple protocols) 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. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Scientific and 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 expenses; and (3) sufficiently staffed across the participating institutions. For research involving multiple sites, a plan for analysis of pooled data will be developed by the Steering Committee.

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

7. Reporting the study findings. 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 DHS, 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.

8. Any involvement of a third party in the study, including access to any study data; study results; using the name of the study; or the name of the NIH or NIDDK, is permitted only after concurrence by the NIDDK Program Official who may consult with others at NIH including the NIDDK Technology Advancement Office.

9. 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.

10. 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.

11. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biological samples collected in large, multi-site studies funding by NIDDK. The Principal Investigator or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution, as appropriate and consistent with achieving the goals of the program. In addition, if applicable, the Principal Investigator 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 an 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/policydata 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) as well as the NIDDK policy for data sharing in multi-center and large single-center studies http://www.nidd.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.

12. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 7, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the sponsor 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/fdaa.html. In addition grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issues by the International Committee of Medical Journal Editors (http://icmje.recommendations.browse/publishing-and-editorial-issues/clinical-trial-registration.html).

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

An NIDDK Project Scientist with substantial involvement will:

1. Serve as the contact point for all facets of the scientific interaction with the awrdee(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 Scientists or Project Coordinator, 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, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator will be a full participant and voting members of the Steering Committee and, if applicable, subcommittees.

3. Serve 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. Have 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 NIDDK Project Scientist or Project Coordinator 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 Project Coordinator 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) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

The NIDDK Program Official identified in the Notice of Award will:

1. Interact with the Principal Investigators 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, Observational Study Monitoring Board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.

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

3. 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 the 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; (f) low likelihood of showing a benefit of the intervention (futility); and (g) 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.

4. Make 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 high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.

5. Appoint an independent Observational Study Monitoring Board; this Board (OSMB) will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the OSMB.

Areas of Joint Responsibility Include:

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

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, 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 the by 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 Investigators, including those of the Scientific and Data Coordinating Center 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 the 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, in consultation with the Steering Committee. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the OSMB established by the NIDDK and by interacting closely with the awardees during protocol development and implementation.

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.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Tracy L. Rankin, Ph.D., M.P.H.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4748
Email: [email protected]

Jason Hoffert, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-496-9010
Email: [email protected]

Charlette Kenley
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8847
Email: [email protected]

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.

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 Part 75.