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)

Funding Opportunity Title

Limited Competition for the Continuation of Epidemiology of Diabetes Interventions and Complications (EDIC) Study Clinical Research Center (Collaborative U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-DK-16-508

Companion Funding Opportunity

RFA-DK-16-509, U01 Research Project - Cooperative Agreements

Number of Applications

Only one application per institution is allowed, see Section III. 3. Additional Information on Eligibility.

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

93.847

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to continue to follow the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort through a collaborative cooperative agreement. EDIC is an observational study that was launched at the completion of the Diabetes Control and Complications Trial (DCCT) trial. The DCCT showed that intensive therapy significantly reduced the risk of diabetes complications compared to conventional therapy. At DCCT completion, all cohort members were taught intensive diabetes therapy. In 1994, EDIC was launched to: (1) evaluate the long-term effects of DCCT intensive therapy, (2) describe the long-term effects of glycemia and other risk factors on diabetes complications, and (3) characterize type 1 diabetes complications by supporting collaborative research to utilize the EDIC cohort as well as its data set and biologic/genetic samples. To date, EDIC has: (1) demonstrated a continued benefit of intensive therapy on the development and progression of diabetes complications, and (2) characterized the development and progression of diabetes complications. The primary purpose of this FOA is to support the EDIC Clinical Research Center to continue follow-up of the EDIC cohort to study the development of complications and the longer term course of type 1 diabetes in a well characterized type 1 diabetes population, including but not limited to cardiovascular disease, mortality, severe microvascular disease (blindness, kidney failure, amputation), neurocognitive impairments, and physical fragility. The EDIC Clinical Research Center will manage and support EDIC Clinical Centers, which are responsible for the conduct of all EDIC core activities as described in the protocol and Manual of Operations and as required by the local Institutional Review Board. The EDIC Clinical Research Center will also facilitate the conduct of all approved EDIC ancillary studies. The Clinical Centers will collect data in accordance with established study procedures and will submit all data and samples to the Biostatistics Research Center and central laboratory and other core facilities as appropriate and as required by the protocol(s). RFA DK-16-509 will support continuation of the EDIC Biostatistics Research Center.

Key Dates
Posted Date

August 1, 2016

Open Date (Earliest Submission Date)

October 8, 2016

Letter of Intent Due Date(s)

October 8, 2016

Application Due Date(s)

November 8, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2017

Advisory Council Review

May 2017

Earliest Start Date

July 2017

Expiration Date

November 9, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research Instructions for 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.


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

This FOA invites an application from the current awardee of the Epidemiology of Diabetes Interventions and its Complications (EDIC) Clinical Research Center to continue research on the EDIC cohort. The application submitted under this FOA is linked to RFA-DK-16-509, which will support the EDIC Biostatistics Research Center.


Following the discovery of insulin in 1921, the role of hyperglycemia in the development and progression of type 1 diabetes microvascular complications (retinopathy, nephropathy and neuropathy) was unclear. The landmark Diabetes Control and Complications Trial (DCCT), launched in 1983, was designed to determine whether intensive type 1 diabetes therapy, compared to conventional therapy, would affect the development and progression of these diabetes complications. A total of 1,441 subjects with type 1 diabetes were randomized (1:1) at 29 North American Clinical Centers to receive intensive therapy, aimed at achieving near-normal glycemia (average hemoglobin A1c of 7% was achieved), or conventional therapy (average hemoglobin A1c of 9% was achieved), aimed at maintenance of clinical well-being without specific glucose targets. The cohort included a primary prevention group, 726 individuals without pre-existing diabetes complications, and a secondary intervention group, 715 subjects with mild retinopathy or mild albuminuria.

In 1993, after a mean follow-up period of 6.5 years, the dramatic beneficial effects of intensive treatment led to DCCT termination one year ahead of schedule. Specifically, intensive therapy reduced the risk of retinopathy, nephropathy and neuropathy by 26-63% compared to conventional therapy. In addition, later analyses of the trial data showed that hyperglycemia was a primary determinant of complications. The DCCT also described the effects of intensive therapy on risk factors for cardiovascular disease, and on neurocognition and quality of life. The DCCT outcomes resulted in universal adoption of intensive therapy as the standard of care for persons with type 1 diabetes.

At DCCT completion, the cohort was young (average 34 years of age) and the duration of diabetes was brief (average 12 years), making it too soon to evaluate macrovascular and severe microvascular complication risks, so in 1994, a DCCT follow-up study, Epidemiology of Diabetes Interventions and Complications (EDIC), was launched. The purpose of EDIC, a multi-center, longitudinal, observational study, was to further utilize the well-characterized DCCT cohort (1297 subjects; 95% of the surviving DCCT cohort) to evaluate the long-term effects of DCCT treatment assignment (by intention-to-treat analysis) and of longstanding disease on the development and progression of complications. During a one year transition period, DCCT conventional treatment participants were taught intensive therapy, and routine diabetes care of all participants was transferred to primary care providers. By EDIC year 6, the DCCT treatment groups no longer differed with respect to hemoglobin A1c level (both averaged 8%). 

Since the initiation of EDIC, cohort members have been evaluated annually for micro- and macrovascular complications. Currently, EDIC is in its 23rd year, and approximately 95% of the surviving DCCT cohort continues to actively participate in follow-up. Intensive therapy has substantially and consistently demonstrated a beneficial impact on the development and progression of microvascular complications. Of note, the early positive effects of intensive therapy on complications (during DCCT) has persisted (reflecting metabolic memory), despite the convergence of hemoglobin A1c levels of the DCCT intensive and conventional therapy groups. Other major long-term findings from EDIC include a reduction in cardiovascular disease risk and mortality for those in the intensive therapy arm. Mortality after 30 years of data collection in 99.2% of the DCCT cohort was 33% lower in the DCCT intensive therapy group compared to the conventional treatment group. Approximately 240 manuscripts, including eight papers in the New England Journal of Medicine, have been published by the DCCT/EDIC study group.

In addition to the many micro- and macrovascular complication assessments performed as part of the core EDIC Study, a number of ancillary projects, funded via separate mechanisms, have also been developed and implemented, including studies addressing urologic, musculoskeletal, autonomic nervous system (gastrointestinal and cardiac) and hearing complications as well as physical functioning.  

This FOA invites an application from the existing EDIC Clinical Research Center to support longer term follow-up of the EDIC cohort as a whole and by DCCT treatment group. Areas of focus will include cognition and depression, physical function and frailty, onset and progression of microvascular disease (including the development of severe microvascular complications), cardiovascular disease and mortality. The goal is to build on the extremely well-characterized DCCT/EDIC cohort that has been studied longitudinally, regularly and meticulously, for between 23 and 33 years. Remarkably, about 95 percent of the living cohort continues to actively participate in study activities. The cohort is now reaching an age and duration of disease which affords an unprecedented opportunity to further assess the aging EDIC cohort as some members progress toward severe microvascular disease, cardiovascular disease and mortality to better define risk and risk factors. In addition, understanding the quality of life issues facing individuals with longstanding type 1 diabetes, such as cognitive impairment, depression, physical limitations and frailty, is of great importance. It is critical to study the complicated risk factors that contribute to the development and progression of these disabling diabetes complications.

The EDIC study group, consisting of investigators and coordinators from the Clinical Centers, Clinical Research Center and Biostatistics Research Center, should collaboratively develop plans for the continued longitudinal study of individuals in the EDIC cohort. The study group should continue to encourage ancillary studies to test novel hypotheses using the EDIC cohort, samples and data.

Study Group Components

1.  Clinical Research Center

There will be a single EDIC Clinical Research Center. The Clinical Research Center will provide fiscal support and coordination for all EDIC Clinical Centers. The Clinical Research Center will establish and maintain subcontracts with each of the EDIC Clinical Centers, and will manage budget preparation and invoice processing for all Clinical Centers. The Clinical Research Center will provide Clinical Center support during Clinical Center staff transitions and will be responsible for assessing study-wide needs at the Clinical Centers for the conduct of core activities and ancillary studies.

The Clinical Research Center will ensure that Clinical Centers conduct EDIC studies in accordance with established study procedures, and that all samples and data are submitted to the Biostatistics Research Center, central laboratories, central reading centers, and other core facilities as appropriate and required by the protocol.

The EDIC study group will have exclusive access to data from the EDIC study population for a defined period, according to NIDDK data sharing policies. All study data analyzed for publication of the study outcome(s) are expected to be provided to the NIDDK Repository so that it can be shared within six months of the publication date for primary outcome publication or within two years of the date that the database is locked for analysis, whichever occurs first, as appropriate and consistent with achieving the goals of the program. All data analyzed for publication of the secondary outcome(s) are expected to be provided to the NIDDK Repository so that it can be shared within two years of the date that the database for these outcomes is locked for analysis, consistent with achieving the goals of this program. In addition, data from each five-year project period must be provided within two years of completion of that project period. The EDIC Steering Committee will abide by their established policies under which ancillary studies may be conducted while the study is ongoing, consistent with applicable laws, regulations and policies.

2.  Biostatistics Research Center

The EDIC Biostatistics Research Center is being solicited in a companion FOA (RFA-DK-16-509). The Biostatistics Research Center will work with the Clinical Research Center and Clinical Centers to develop and implement core studies and facilitate ancillary studies. The Biostatistics Research Center will provide biostatistical and analytic expertise and conduct analyses and interpretation of the laboratory and clinical data in conjunction with investigators at the Clinical Research Center and Clinical Centers. The Biostatistics Research Center will be responsible for guiding development of the statistical analysis for the study as a whole and for each manuscript reporting prespecified primary and secondary outcomes. The Biostatistics Research Center will also be responsible for establishing all scientific collaborations for specialized outcomes measuring complications of diabetes.

In addition to conducting the research described above, the Biostatistics Research Center is responsible for the collection and management of all clinical and laboratory data. The Biostatistics Research Center will be responsible for ensuring subject confidentiality and safety and quality control. The Biostatistics Research Center will conduct training and certification of study staff in concert with reading centers and the central biochemistry laboratory, as needed, and maintain and update the manual of operations. The Biostatistics Research Center will oversee implementation of and adherence to the study protocol. The Biostatistics Research Center will coordinate communication among and with the Clinical Research Center and the Clinical Centers.

The Biostatistics Research Center will be responsible for movement of biologic samples and other study-generated materials from the Clinical Centers to the central laboratory(ies), and subsequently to the NIDDK Repository (samples), where samples will be stored for future analysis. The Biostatistics Research Center will similarly ensure the flow of radiographic tests and other collected data and materials to the appropriate core facilities. The Biostatistics Research Center will also work with the NIDDK Data Repository to prepare all EDIC data for eventual archiving and distribution.

The Biostatistics Research Center will prepare appropriately detailed reports to the EDIC Steering Committee, Observational Safety and Monitoring Board (OSMB), External Evaluation Committee (EEC) and NIDDK staff at regular intervals. The Biostatistics Research Center will be responsible for the planning and logistical coordination of meetings of the Steering Committee and its subcommittees, and will assist NIDDK with logistical coordination of OSMB and EEC meetings.

3.  Clinical Centers

The Clinical Centers are responsible for the conduct of all EDIC core activities as described in the protocol and Manual of Operations and as required by the local Institutional Review Board. The Clinical Centers will also facilitate the conduct of all approved EDIC ancillary studies.

The Clinical Centers will collect data in accordance with established study procedures and will submit all samples and data to the Biostatistics Research Center and central laboratory and core facilities as appropriate and as required by the protocol(s).

4.  Steering Committee

The primary governing body of the study will be the Steering Committee, comprised of the PDs/PIs of the Biostatistics Research Center, the Clinical Research Center, each Clinical Center, each Central Reading Center, the Clinical Center Study Coordinators and the NIDDK Project Scientist.

The Steering Committee will develop policies and procedures for the EDIC study group, and ensure that these policies are properly implemented. These may include procedures for modification of study design, use of study samples and data, approval of ancillary studies, publication and presentation of study findings, monitoring study progress, determining completeness and quality of data collection and other performance measures.

5.  Project Scientist

The NIDDK Project Scientist will assist the Steering Committee in carrying out the EDIC study. The Project Scientist will provide scientific support to awardees' activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications and overall performance monitoring.

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

Renewal

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit up to $8 million in Fiscal Year 2017 to support the continuation of EDIC under RFA-DK-16-508 and RFA-DK-16-509. It is expected that one award will be made for the Clinical Research Center under this FOA, and that one award will be made to the EDIC Biostatistics Research Center under the companion RFA-DK-16-509.

Award Budget

The application budget is limited to $3.5 million per year in direct costs for the entire project period (exclusive of subcontract F&A). Budgets should reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is five 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

This FOA is limited to the current awardee of the EDIC Clinical Research Center.

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

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.

Eligible Individuals (Program Director/Principal Investigator)

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 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.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

Section IV. Application and Submission Information
1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research Instructions for 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.

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:

  • 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, preferably electronically, should be sent to:

Michele L. Barnard, Ph.D.
Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
6707 Democracy Boulevard, Room 7353
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: 301-594-8898
Email: NIDDKLetterofIntent@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related set of collaborative applications, the titles of each application in the set must have the following format: a 1/N indicator + identical title (e.g., 1/2 where the 1/2 means that this site is 1 of 2 sites in the set. The other site will be labeled 1/2.) A set of applications is defined as all applications submitted in response to this FOA as well as the companion FOA (RFA-DK-16-509). Titles of all collaborative applications must be identical except as follows: Applications submitted in response to this FOA must include "Clinical Research Center" at the end of the title; the application submitted in response to RFA-DK-16-509 should include "Biostatistics Research Center" at the end of the title. The numbering order of the collaborative applications in the consortium is at the discretion of the applicants. Titles may not exceed 200 characters in length, including the tag (e.g., 1/2) at the beginning of the title.

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Other Attachments: The following items should be included as attachments.

1. Clinical Protocol Synopsis

The file name "Clinical Protocol Synopsis.pdf should be used and will be reflected in the final image bookmarking for easy access to reviewers.

The clinical protocol synopsis must include the following information:

  • Description of the study cohort, in aggregate, for the entire study
  • Table showing the demographics of the subject population at every site;
  • Planned approaches to be used for subject adherence and retention as well as potential changes to the study population (for example, due to aging);
  • Description of how data from the sites will be obtained, managed and protected;
  • Descriptions of all clinical, laboratory, physiological, and behavioral tests to enable the research questions to be answered; and
  • Description of the data management and quality control plan, including methods for monitoring the quality and consistency of the data collection, and data confidentiality and subject privacy

2.  Statistical Analysis Plan

The filename "Statistical Analysis Plan.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

The applicant should describe the statistical methods to be used, including the sample size and power calculations, plans for primary and secondary analyses, and pre-specified interim analyses. Although applicants may only request 5 years of funding, power calculations may be provided for more than 5 years of follow-up, if appropriate. If optimal power would be achieved with longer follow-up, the Biostatistics Research Center should provide plans for futility analysis as soon as possible and no later than at the end of year 3 of the project period that would allow NIDDK to make a determination about whether to request applications to extend the follow-up for an additional project period.

Applications that lack the Statistical Analysis Plan are incomplete and will not be peer reviewed.

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: The Specific Aims must be identical in each of the applications that are linked as a collaborative set.

Research Strategy: Each application must contain a Research Strategy that clearly describes those aspects of the project that are common to both sites of the collaboration. The Research Strategy must be identical across the linked applications, with the exception of the section under the header "Elements Unique to this Site." In this subsection, the Clinical Research Center PD/PIs should describe their unique contribution(s) to the study.

The common Research Strategy section should include:

1.  A discussion of the significance of the problem being studied, the need for the study, and the potential impact of the results of the study;

2.  A concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the study;

3.  A discussion of studies that led to the proposed studies and information or data from preliminary studies that address the need for and feasibility of the proposed studies; and

4.  A brief acknowledgement of responsibilities as part of the multi-center collaborative project.

In addition, the following should be thoroughly addressed in the research plan:

1.  Evaluation of the long-term effects of intensive versus conventional therapy, including the role of glycemic and non-glycemic risk factors on cognition/dementia, depression, age-sensitive morbidities and quality of life;

2.  Evaluation of the long-term effects of intensive versus conventional therapy, including the role of glycemic and non-glycemic risk factors on physical function and frailty in the context of diabetes and aging;

3.  Analysis of risk factors, protective factors and mechanisms associated with severe/advanced microvascular complications (vision loss, end stage kidney disease, amputation), and evaluation of whether the risk factors for these differs from those identified during earlier stages of disease, and identification of intervention targets according to diseases stages;

4.  Analysis of risk factors and mechanisms associated with cardiovascular disease and mortality;

5.  Development of new research approaches to measure the vector of disease progression in type 1 diabetes to create tools to forecast individual and combined/multiple outcomes to generate guidelines for complications screening;

6.  The study of long-term health-related quality of life and economic consequences of advanced type 1 diabetes complications and the development of new metrics to assess overall health and disease over time in individuals with type 1 diabetes;

7.  The use of control groups, for core and ancillary studies, including the justification for use of a spousal/partner control when appropriate and of historical control data when indicated (including specifics regarding the historical control data to be used);

8.  Strategy to ensure continued subject adherence to study visits and procedures; and

9.  The inclusion of junior investigators in the conduct of EDIC.

A unique Clinical Research Center section should include a description of the study organization and administration, including, but not limited to:

1.  The committee structures needed to manage the complexity of the study; and

2.  The oversight, responsibilities and coordination of clinical sites proposed as subcontracts to the Clinical Research Center.

In this section, there should be a sufficient description of the items listed above to permit thorough evaluation of the Research Strategy. Technical details contained in the clinical trial synopsis, statistical analysis plan, and data and safety monitoring plan can be referenced from within the Research Strategy section, in order to avoid the duplication of text.

The Clinical Research Center applicant must describe plans including, but not limited to:

1. Core Project Support - Plans for continuation and analysis of ongoing core study assessments as well as plans for the development, implementation and analysis of new core study activities.

2.  Ancillary Study Support - Plans for support of ongoing and planned ancillary study activities.

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 Sharing Plan.

The NIDDK has established Central Biosample, Genetic and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The investigator(s) should be prepared to transfer all data and samples to the Repository at scheduled study time points (which should be specified in a unique Biostatistics Research Center section of the application) and at the conclusion of the study, consistent with achieving the goals of the program. The study group will have exclusive access to data for a defined period, according to NIDDK data sharing policies (http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf).

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. The study protocol may be attached as an appendix.

PHS Inclusion Enrollment Report

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

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. 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.

7. Other Submission Requirements and Information

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. 

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at NIDDKLetterofIntent@mail.nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 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? Is there a strong scientific premise for the project? 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?  

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/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?   

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? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate 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?  

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?   

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 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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

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.

Vertebrate Animals

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.

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 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)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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

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 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 (NIDDK) 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.
3. Anticipated Announcement and Award Dates

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.

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 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.

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.

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.

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.

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.

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 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 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 sites, 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.  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 DHHS, 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

archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The PI or his/her designee will coordinate with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution, consistent with achieving the goals of the program. In addition, if applicable, the 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   (https://grants.nih.gov/grants/policy/data_sharing/  and,

https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals , and https://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 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/fdaaa.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 issued by the International Committee of Medical Journal Editors (http://icmje.org/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 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, participate 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. 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 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) 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 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.

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

5. Appoint 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

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. An Observational Study Monitoring Board (OSMB) will be established for observational/epidemiologic studies. These Boards will review study progress, safety data and interim results, as appropriate, 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 Research Performance Progress Report (RPPR) 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.

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.

Section VII. Agency Contacts

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

Application Submission Contacts

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: https://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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Scientific/Research Contact(s)

Ellen Leschek, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-402-8291
Email: LeschekE@extra.niddk.nih.gov

Peer Review Contact(s)

Najma Begum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8897
Email: begumn@csr.nih.gov

Financial/Grants Management Contact(s)

Diana O'Donovan
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-301-594-8868
Email: odonovand@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 Part 75.

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