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

Research Using Subjects From Selected Type 1 Diabetes Clinical Studies (Living Biobank) (DP3)

Activity Code

DP3 Type 1 Diabetes Targeted Research Award

Announcement Type

Reissue of PAR-14-064

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR-14-258

Companion Funding Opportunity

None

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

93.847 

Funding Opportunity Purpose

This Funding Opportunity Announcement invites applications for ancillary studies that use subjects enrolled in (or screened for participation in) the Type 1 Diabetes TrialNet clinical trials network, or for ancillary studies that use subjects enrolled in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC). Studies are expected to generate scientific discoveries on disease mechanisms, disease pathogenic processes, and biomarkers of disease progression or clinical responses of type 1 diabetes and its complications. This FOA is not intended to fund clinical trials with endpoints for clinical efficacy (including but not limited to C-peptide preservation.)

Key Dates
Posted Date

June 11, 2014

Open Date (Earliest Submission Date)

October 20, 2014

Letter of Intent Due Date(s)

October 20, 2014

Application Due Date(s)

November 20, 2014, by 5:00 PM local time of applicant organization.

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 2015

Advisory Council Review

May 2015

Earliest Start Date

July 2015

Expiration Date

November 21, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.



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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
 
Purpose

The National Institute of Diabetes and Digestive and Kidney Diseases seeks to accelerate the pace of scientific research towards prevention, more effective treatment, or cure of type 1 diabetes and its complications. To this end, NIDDK is committed to providing access to research resources which will increase our understanding of type 1 diabetes pathogenesis, and pathogenesis of its complications, in humans. This opportunity is intended to fund projects using subjects who have been phenotypically and genetically characterized for risk of developing type 1 diabetes through the Type 1 Diabetes TrialNet Pathway To Prevention clinical research network, and projects using subjects currently enrolled and followed for diabetic complications in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC). To assist applicants for this and other related funding opportunity announcements, two webinars are planned. Applicants should visit the NIDDK website for more information about registering for one of these informational webinars.

For examples of projects funded under similar FOAs, use the NIH Research Portfolio Online Reporting Tool (RePORTER). Enter the FOA designations (PAR-13-028 or PAR-11-349 or PAR-14-064, separate queries) in the field labeled FOA in the "Project Details" section, clear the Fiscal Years field in the top right corner of the query page, and run the query to view descriptions of awarded grants.

Type 1 Diabetes TrialNet

The Type 1 Diabetes TrialNet is an international network of investigators, clinical centers, and core support facilities that conducts research to advance knowledge about type 1 diabetes and to test strategies for its prevention and early treatment. TrialNet supports the development and implementation of clinical trials of agents aimed at preventing the disease in at-risk patients and slowing the progression of type 1 diabetes in new onset patients. The Network’s “Pathway To Prevention Study” enhances understanding of how the disease develops in individuals at risk and thus helps in the formulation of future trials. The Pathway To Prevention Study provides the basis for risk assessment and recruitment of at-risk subjects into clinical trials aimed at preventing the disease in susceptible individuals. Identification of subjects at risk for type 1 diabetes requires enormous effort. Currently TrialNet screens nearly 20,000 relatives of those with type 1 diabetes.  This FOA is intended to provide a means of support for mechanistic studies using the population of subjects screened and monitored in TrialNet, to obtain maximum value from this effort.

Currently there are three ongoing clinical trials for prevention in TrialNet. One is the Oral Insulin Trial which tests the ability of insulin taken orally to prevent the disease in subjects with moderate risk of disease. The second is the Anti-CD3 Prevention Trial which tests whether a course of teplizumab therapy can prevent the disease in high risk subjects. The third is the Abatacept for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives at Risk for T1D which tests whether abatacept treatment can prevent people with moderate risk from progressing to early stage metabolic dysfunction. Other trials are planned and could be in progress at the receipt date for this FOA.  See the TrialNet website for more detailed information: http://www.diabetestrialnet.org/researchers/index.htm.

TrialNet screens first and second degree relatives of persons with type 1 diabetes for evidence of autoimmunity (one or more serum autoantibody). Positive subjects are offered further testing using genetic and metabolic tests, and are recruited into ongoing clinical trials or studies, or the observational Pathway To Prevention study. Subjects in the Pathway To Prevention are followed clinically with metabolic and autoantibody tests, as well as serum, RNA, plasma, and peripheral blood mononuclear cells (PBMC) collections every six months. Samples are stored in an archive. A smaller number of control subjects (autoantibody negative relatives of people with type 1 diabetes) are also enrolled and followed in the Pathway To Prevention. Access to samples from the archive, and funding for such studies, are available by application to different FOAs as listed below. This FOA is for additional tests on subjects, or the collection of special “on demand” samples at any point in the staging process, or at the regular visits or before and after a brief and safe intervention. A more detailed description of the schedule of assessments in the TrialNet Pathway To Prevention Study and the ongoing and approved TrialNet clinical trials and ancillary studies is provided here: http://www.diabetestrialnet.org.

Studies can be cross-sectional or longitudinal. Mechanistic studies that require a brief and safe intervention may also be proposed in at risk populations. Opportunities are also available to access subjects currently participating in prevention trials within TrialNet, as long as studies funded by this FOA do not interfere with their recruitment and participation in trials.

Exploratory research related to understanding type 1 diabetes pathogenesis in humans is encouraged if the question is significant and the investigators are well qualified.  Small exploratory pilot studies to gather information relevant to type 1 diabetes prediction and prevention are especially encouraged.

This FOA is NOT intended to fund clinical trials to test efficacy of interventions for type 1 diabetes prevention or treatment.  Efficacy endpoints include C-peptide preservation or insulin dose, for example.  Other funding mechanisms, including TrialNet (http://www.diabetestrialnet.org/researchers/index.htm ), are available for the development and implementation of clinical trials with clinical efficacy endpoints.  Clinical pilot studies involving safe interventions of short duration, involving a minimal number of subjects, and using mechanistic endpoints, are allowed under this FOA. Large, collaborative and coordinated projects that make use of multiple PDs/PIs are encouraged.

This FOA is NOT intended to fund studies using samples currently stored in the TrialNet or NIDDK or any other samples repository.  Other funding opportunities (PAR-09-247, and PAR-13-228 and PAR-14-257) are available for ancillary studies using non-renewable longitudinal stored samples.

Examples of possible projects include but are not limited to:

  • New technology for measurement of biomarkers of type 1 diabetes in peripheral blood, including correlates of: disease susceptibility, environmental triggers, autoimmunity, disease progression (including measures of beta cell mass or function);
  • Measurements of islet cell function and insulin resistance in persons at risk, including glucose clamps and measurements of glucagon response;
  • Minimally invasive, targeted imaging of pancreatic inflammation or beta cell mass in persons at high and low risk of developing type 1 diabetes, with or without a short course of anti-inflammatory intervention;
  • Evaluation of vaccine responses in persons with type 1 diabetes risk; including effects of vaccines on metabolic as well as immunological measures;
  • Evaluation of changes in immune parameters in response to short term treatment with immunomodulatory drugs;
  • Measuring functional correlates of type 1 diabetes risk, assays requiring special collection techniques or specimens not currently collected in TrialNet.

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study

EDIC (1994-present) is an observational follow-up study of the cohort from the Diabetes Control and Complications Trial (DCCT, 1983-93).  The DCCT, established through an Act of Congress, addressed the role of diabetes control, and in particular hyperglycemia, on long-term diabetic complications. 1441 type 1 diabetic individuals age 13-39 years were recruited from 29 clinical centers across the U.S. and Canada. The cohort, consisting of 726 primary prevention subjects with no pre-existing microvascular complications and 715 secondary intervention subjects with mild retinopathy and <200 mg albuminuria/24 h, were randomly assigned to receive either intensive therapy aimed at near normal glycemia or conventional therapy aimed at maintenance of clinical well-being with no specific glucose targets. The objective was to determine whether intensive therapy would reduce the development or progression of retinopathy primarily, and secondarily nephropathy and neuropathy.  The randomized phase of the study was terminated in 1993 by the Data and Safety Monitoring Board after a mean follow-up of 6.5 yrs, owing to the overwhelming beneficial effects of intensive diabetes therapy. Compared with the conventional therapy which achieved a median HbA1c level of ~9%, intensive therapy with at least three insulin injections per day or insulin pump therapy, guided by self-monitored glucose levels, achieved a median HbA1c of ~7% and reduced the development and progression of early stages of long-term complications by 35-76%.

The relatively young age (mean age of 33 years) and brief duration of diabetes (12 years) of the cohort at DCCT study-end in 1993 precluded exploration of the effects of intensive compared with conventional therapy on the more advanced sequelae of microvascular disease or on cardiovascular disease (CVD). EDIC (1994-present) was launched as an observational follow-up study of the DCCT, using the same methods and annually following 95% of the surviving original cohort representing 1326 participants. Participants are seen in 27 of the original 29 clinical centers (2 in Canada, 25 across the U.S.). Mean age of the participants is currently 53 years.

Overarching goals of EDIC are to 1) determine the long-term effects of the original interventions on advanced complications, including CVD; 2) delineate the modern-day clinical course of diabetic complications including the interactions among complications and co-occurrence of complications; 3) explore the pathophysiologic mechanisms that underlie the development and progression of microvascular, neurologic, and cardiovascular complications, and 4) define the long-term economic impact of intensive therapy.

Annual evaluations include a history and physical examination, ECG, Doppler evaluation of brachial:ankle pressure, a standardized neurologic examination, measurement of A1c and serum creatinine, documentation of hypoglycemia and diabetic ketoacidosis; lipids, albumin excretion/creatinine clearance, dietary assessment, and quality of life are measured every other year. An eye exam measuring visual acuity and including fundus photography is completed every four years. Episodically, a carotid ultrasound is performed.

Other ancillary study procedures and assessments that have been conducted include coronary calcium CT scans, cardiac MRIs, nerve conduction studies, cognitive impairment testing, urologic and sexual function assessment, genetics studies through family/association studies and genome-wide association study, epigenetic studies, measurement of haptoglobin, measurement of skin advanced glycation end-products by fluorescence spectroscopy, cheiroarthropathy assessment, hearing impairment assessment, and a survey to study reasons for the long-term high participation rate. 

This FOA provides a means of accessing this unique population being followed in DCCT/EDIC.

Proposed studies can be cross-sectional or longitudinal (within the time frame of the award).

Applicants may propose to perform tests on subjects and/or collect samples "on demand" at regularly scheduled EDIC study visits.

Studies funded by this FOA must not interfere with recruitment and participation of subjects in ongoing core and ongoing ancillary studies being conducted in the DCCT/EDIC.

This FOA is NOT intended to fund studies using DCCT/EDIC samples currently stored in the NIDDK or any other samples repository.  Other funding opportunities (PAR-09-247, and PAR-13-228  and PAR-14-257) are available for ancillary studies using non-renewable longitudinal stored samples. 

Examples of projects include but are not limited to:

  • Evaluation of blood glucose variability as an independent risk factor for diabetic complications;
  • Evaluation of adverse outcomes or predictors of hypoglycemia;
  • Use of novel technologies to elucidate pathogenesis of complications;  
  • Evaluation of conditions such as bone disease and fractures, or other disorders that may be associated with diabetes in the DCCT/EDIC cohort, and correlates of these measures with DCCT treatment, glycemia, and other demographic, clinical, biochemical, behavioral and environmental factors;
  • Identification of biomarkers predictive of development of diabetes complications. 
Human Subjects Protections

In many studies proposing to collect samples at centers and utilize the samples in the applicant's lab, the applicant can remain blinded to subject identity using masking identifiers by the relevant study's Coordinating Center. However, if subject identity cannot be blinded, or an intervention is planned, a plan for human subjects protection including local IRB review and review by Data and Safety Monitoring Board (DSMB) or Observational Study Monitoring Board (OSMB) may be required (see NIH guidelines for clinical research) (see also below under review criteria). If review by an external board is required, applicants may use the established TrialNet DSMB or DCCT/EDIC OSMB.

All investigators are strongly advised to visit the TrialNet website http://www.diabetestrialnet.org/researchers/index.htm or the DCCT/EDIC website https://edic.bsc.gwu.edu/web/edic/edic-potential-collaborators and to contact NIDDK staff (listed below) for assistance in applying to this FOA.

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

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 fund an estimate of 2-4 awards, corresponding to a total cost of $7,000,000 for FY 2015, contingent upon the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to a total cost of $7,000,000 but need to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is three years.   

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

  • To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
  • Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
  • Of an application with a changed grant activity code.
Section IV. Application and Submission Information
1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

  • 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 preferably electronic letter of intent should be sent to:

Dianne M. Camp, Ph.D.
Scientific Review Officer, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Fax: (301) 480-3505
Email: campdm@mail.nih.gov

Page Limitations

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

Required and Optional Components

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

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.

Estimated Project Funding: Enter the budget request here. This number should include total costs (direct and indirect) for the entire project period. Note that a detailed budget cannot be accepted in the application; it will be requested after the initial review.

It is expected that applications will span a wide range of budgetary requirements, from small studies utilizing few subjects to larger studies with more expensive testing.  Small exploratory studies are encouraged. 

Applicants should request, in addition to funding for their own lab, funds for selected costs incurred by the relevant Coordinating Center, specifically related to the proposed study and outside of normal screening and monitoring. For example, if a study requires an additional collection at the next scheduled monitoring visit, there will be no need to budget for costs related to the scheduled visit, but some of the costs of obtaining the additional samples should be requested (i.e., payment for a blood draw on a capitated basis, cost for a specific collection tube, and cost of shipping samples to the assay lab). Studies that require additional visits outside of those normally scheduled will need to budget for the costs associated with additional visits, including patient travel. If the proposed study will require subjects to visit to a specific location for a specific test (for example, an imaging study), patient travel should be included in the request. No costs should be requested for staff salary at the consortia's clinical sites. Costs associated with data collection (case report forms) for data types currently collected do not need to be requested, but if the data or sample collected is new, some costs should be requested. Costs budgeted for Coordinating Center activities are only estimates.  Exact costs will be determined in negotiation with NIH program staff for those applications with an Impact score within funding range. Tables are provided at the TrialNet public website (http://www.diabetestrialnet.org/researchers/index.htm) to assist applicants in estimating these extra costs, and applicants for access to DCCT/EDIC subjects should contact NIDDK Program staff listed below and visit DCCT/EDIC website at https://edic.bsc.gwu.edu/web/edic/edic-potential-collaborators for additional information.

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.  

SF424(R&R) Senior/Key Person Profile

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:

Research Strategy: Applicants must explain how the proposed research will take advantage of the associated clinical and phenotypic data and why the proposed research specifically requires subjects from TrialNet or from DCCT/EDIC. Applicants must describe the data that will be needed to select subjects and/or to analyze results obtained by their project.

The Research Strategy should include:

  • Background and rationale for study; include justification for requesting access to specific subjects as well as the advantage of these subjects compared to other sources of similar subjects.  Applicants planning to combine the results from the proposed study with those obtained from other studies, should explain how the requested subjects will fit in with the overall study design.
  • Specific objectives, including how the results would be integrated with other study results, and the impact of the results on understanding disease pathogenesis, progression, or potential response to treatment;
  • Study details, including the number of subjects required and subject characteristics. Include a clear justification for the number of subjects and amount of sample being requested.  In all cases, applicants should only request the minimum number of subjects and volume of sample needed for the study.
  • Description and justification for any essential controls obtained through the relevant consortia or locally;
  • Amount and type of new samples to be collected if appropriate, variability and quality control characteristics of any proposed assay or test, expected effect sizes and group differences, a statistical plan with calculations to demonstrate that the number of subjects and samples will be sufficient to answer the question; include relevant preliminary data demonstrating the applicant’s experience with the assay or technique that will be used with the requested subjects/samples, including QA/QC data, if available.
  • Data analysis: Provide a detailed plan for data analysis. Include a brief summary of the team’s expertise and experience and evidence that they can handle the analysis proposed, or a request for assistance in data analysis from the study group's Biostatistics Center.
  • Plans for sample management, including return to the NIDDK repository of any unused specimens; and
  • Plans for data management. Describe how the accompanying phenotypic data, as well as the data from sample analysis, will be managed.  For example, who will have primary responsibility for organizing, storing, and archiving the data?  Who will maintain computer data files and make needed work files available to those who will analyze the data?  How will the privacy of information of beneficiaries in the files be guarded and guaranteed?

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

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Applicants are expected to return data derived from analysis of subjects to the data coordinating center for the relevant NIDDK consortium, or the NIDDK Data Repository, along with appropriate quality measures. The plan should acknowledge the expectation to follow NIDDK instructions to return the phenotypic data and any unused samples to the relevant NIDDK consortium or repository by one year after the period of award of this project.

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.

Planned Enrollment Report

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

PHS 398 Cumulative Inclusion Enrollment Report

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the 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.

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 by NIDDK program and review staff. Applications that are incomplete will not be reviewed.

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at fc15y@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? 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? Will the study increase understanding of disease pathogenesis, progression, or potential response to treatment?

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? 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? Is access to these specific subjects, as compared to other sources of similar subjects and/or samples (if available), well-justified?  Is there a clear justification for the number of subjects and amount of sample being requested? Is the statistical plan adequate to demonstrate that the number of subjects and samples will be sufficient to answer the question?

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines 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.
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

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

Section VI. Award Administration Information
1. Award Notices

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.      

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Scientific/Research Contact(s)

For TrialNet:

Lisa M. Spain, Ph.D.
National Institute of Diabetes Digestive & Kidney Diseases (NIDDK)
Telephone: 301-451-9871
Email:spainl@niddk.nih.gov

For DCCT/EDIC:

Catherine C. Cowie, Ph.D., MPH 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8804
Email:  cowie@nih.gov

Peer Review Contact(s)

Dianne M. Camp, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7682
Email: campdm@mail.nih.gov

Financial/Grants Management Contact(s)

Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7794
Email: toddle@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. This FOA is supported under a Special Statutory Program for Type 1 Diabetes Research via PL 113-93 (Section 204), "The Protecting Access to Medicare Act of 2014".

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