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 Biosamples from Selected Type 1 Diabetes Clinical Studies (DP3)
Activity Code	DP3 Type 1 Diabetes Targeted Research Award
Announcement Type	Reissue of PAR-11-350
Related Notices	January 7, 2014 - This PAR has been reissued as PAR-14-065. November 30, 2012 - See Notice NOT-DK-13-003. Notice of Correction Regarding Resubmissions and Budget Instructions.
Funding Opportunity Announcement (FOA) Number	PAR-13-013
Companion Funding Opportunity	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.847
Funding Opportunity Purpose	This FOA invites applications for ancillary studies using archived samples from the DCCT/EDIC, DPT-1, TrialNet, and GoKind type 1 diabetes clinical trials and studies. Ancillary studies are expected to generate scientific discoveries on type 1 diabetes primary pathogenesis or the pathogenesis of complications, and biomarkers of disease progression or clinical responses to interventions.

Posted Date	October 30, 2012
Open Date (Earliest Submission Date)	March 2, 2013
Letter of Intent Due Date(s)	March 2, 2013
Application Due Date(s)	April 2, 2013, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July, 2013
Advisory Council Review	October, 2013
Earliest Start Date	December, 2013
Expiration Date	April 3, 2013
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.

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

The NIDDK seeks to accelerate the pace of scientific research towards more effective treatment and prevention of type 1 diabetes and its complications. To this end, NIDDK is committed to providing access to research resources including biosamples repositories and databases from type 1 diabetes clinical trials. This activity will support investigations on non-renewable (non-DNA) samples generated by selected studies and clinical trials. Potential applicants are strongly advised to read this notice carefully and to contact program staff prior to preparing an application.

There are two ways to access samples. One is through the NIDDK Central Repository (www.niddkrepository.org) which contains samples from the following type 1 diabetes clinical trials: Type 1 Diabetes Prevention Trial- 1 (DPT-1), Genetics of Kidneys in Diabetes (GoKinD), and Diabetes Control and Complications Trial / Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC samples collected though 2006). The second way to access samples is through one of the following NIDDK-funded consortia:

Type 1 Diabetes TrialNet, (http://www.diabetestrialnet.org/index.htm); or the

Epidemiology of Diabetes Interventions and Complications EDIC (samples collected before and after 2006), (https://edic.bsc.gwu.edu/.

This opportunity is limited to research using samples from the clinical trials or studies listed herein. Funding or access to samples will NOT be provided for assay development or exploratory animal models research. Investigators should propose to test scientifically meritorious hypotheses related to the clinical trial’s goals. Applications should provide a strong scientific justification, evidence of assay validation and support for laboratory performance at the highest quality standards.

Studies using NIDDK Repository-held samples (DPT-1, GoKind, DCCT/EDIC) will be reviewed both for access approval and funding at the same time through this FOA. Applicants must visit the NIDDK Repository https://www.niddkrepository.org/niddk/jsp/public/sampleInstruction.jsp, register for a login and password, and make a preliminary application for access to samples. The Repository will then provide a standardized report which will indicate that samples are present in sufficient number and quantity or volume for the study. This report must be included with the grant application or the application will be considered incomplete and will be returned without review.

Applications that propose to use consortium-controlled samples (TrialNet, DCCT/EDIC samples collected before and after 2006) must include a document that clearly indicates that the consortium has granted approval for access to the samples. Applicants must apply to the consortium through the relevant ancillary studies application process (links below) with sufficient time for consortium review prior to the FOA receipt date (at least 6 weeks prior to receipt date). This letter must be included with the grant application or the application will be considered incomplete and will be returned without review.

The FOA is expected to promote scientific discoveries on disease mechanisms, disease pathogenic processes, and biomarkers of disease progression or clinical responses. Applicants must explain how the proposed research will take advantage of the associated clinical and phenotypic data, and why the proposed research specifically requires samples from the selected trial or clinical study. This FOA will provide funding to support scientific collaboration among assay providers from outside of the clinical trials networks and clinical and laboratory scientists and biostatisticians within NIDDK’s consortia listed above. Consortia member scientists are encouraged to submit responsive applications, but they must also have documented access to consortium-controlled samples through the relevant process.

Budgetary information is required. It is expected that this FOA will generate applications with a wide range of budgetary requirements, from small studies utilizing few samples to larger studies with more expensive testing. Budgets should include repository charges (see the repository website https://www.niddkrepository.org/niddk/home.do for access charges by sample type).

Plans for sample and data management, safe storage, and plans for returning any unused specimens, plans for data sharing (data must be shared with the consortium or the repository source) and future directions. Applicants are expected to return data derived from analysis of samples 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 unused samples to the relevant NIDDK consortium or repository by one year after the period of award of this project.

The following is a brief description of clinical trials and studies with opportunities for samples access and testing.

1. The Diabetes Control and Complications Trial (DCCT) recruited 1,441 type 1 diabetic participants who were randomly assigned to 2 treatment groups, intensive and conventional, for an average of 6.5 years of randomized treatment time. The DCCT ended in 1993 after demonstrating conclusively that intensive treatment reduced the development and progression of diabetic retinopathy, nephropathy and neuropathy, compared to conventional treatment. Subsequently, the Epidemiology of Diabetes Interventions and Complications Study (EDIC) recruited 96 percent of the living participants from DCCT for regular observational follow-up of metabolic and complications status, using similar methods as in the DCCT. The former intensive treatment group continues to exhibit the same reduction in the risks of diabetic complications, starting from a new baseline. This carry-over effect of prior glycemic exposure on the later course of complications (superimposed on the effect of concurrent glycemic exposure) has been called "metabolic memory". Serum, plasma and urine samples have been obtained annually since the DCCT baseline and stored frozen at -70 C. Samples collected through 2006 are available through the NIDDK Repository and may be applied for under this FOA. A data set is available and applicants are urged to obtain and review the data to assist in their preparation of the application. Information for obtaining data and a samples availability report from this study is available on the NIDDK Repository Website: https://www.niddkrepository.org/niddk/home.do.

The ongoing DCCT/EDIC research group also welcomes applications for collaborative studies from any investigator who believes he/she has a research idea that could utilize some of the stored sample collection (serum, plasma and urine) and clinical phenotypic data in an ancillary study. Any proposal would receive initial review by the relevant DCCT/EDIC committees, and would have to abide by the policies and procedures for data sharing and publications described here: http://www.niddk.nih.gov/patient/EDIC/edic.htm.

Possible research topics for DCCT/EDIC biosamples include, but are not limited to:

• Analysis of blood or urine samples for new biomarkers (metabolomic, proteomic, etc.) associated with susceptibility (or resistance) to T1D complications, related to the DCCT intervention.
• Analysis of blood or urine samples for validation of biomarkers that have been discovered through new research on the mechanism of diabetes complications.

2. GoKinD: The Genetics of Kidneys in Diabetes collection (Mueller PW et al. JASN 2006) was created to facilitate research into Type 1 diabetes and the genetic basis of diabetic kidney disease by providing access to data and samples for genotyping. GoKinD created a repository of DNA and clinical information from adults with long-term Type 1 diabetes, with or without kidney disease. Probands had diabetic nephropathy (persistent proteinuria or end stage renal disease) caused by Type 1 diabetes, had Type 1 diabetes for at least 10 years, were diagnosed before age 31, and received insulin therapy without interruption. Controls had persistent normoalbuminuria despite having type 1 diabetes at least 15 years, did not take antihypertensives and had never been treated with ACE inhibitors. All participants contributed DNA, plasma, serum, and urine samples. For 268 of the 930 probands and for 318 of the 939 controls, the equivalent clinical information and saved biological samples are also available for both the mother and father as well as for the probands. A clinical data set is available along with GWAS data and applicants are urged to obtain and review the data to assist in their preparation of the application. Information for obtaining data and a samples availability report, and samples access data sharing policies, is available on the NIDDK Repository Website: https://www.niddkrepository.org/niddk/home.do.

Possible research topics for GoKinD biosamples include, but are not limited to:

• Analysis of blood or urine samples for new biomarkers (metabolomic, proteomic, etc.) associated with susceptibility (or resistance) to diabetic kidney disease.
• Analysis of blood or urine samples to further characterize the role of molecules implicated in the development of diabetic kidney disease.

3. DPT-1: The Diabetes Prevention Type 1 (DPT-1) trial was a multi-center randomized clinical trial to determine if treatment with a common beta-cell auto-antigen (insulin) can delay the onset of Type 1 Diabetes Mellitus (Type 1 DM) in relatives of persons with type 1 diabetes. The protocol for high risk subjects used daily subcutaneous insulin injections and an annual course of intravenous insulin treatment (N. Engl. J. Med, 2002 May 30; 346(22):1685-91), while the protocol for intermediate risk subjects used daily doses of insulin or placebo administered orally (Diabetes Care, 2005 May;28(5):1068-76.) There were over 100,000 relatives of persons with type 1 diabetes screened, and 711 subjects entered either the parenteral or oral arm of the study. Serum samples were collected and will be available from subjects who enrolled in the trial(s), some of whom later developed type 1 diabetes. Samples from a selection of subjects (over 10,000) who were autoantibody negative at screening are also available. A data set is available and applicants are urged to obtain and review the data to assist in their preparation of the application. Information for obtaining data and a samples availability report, and samples access data sharing policies, is available on the NIDDK Repository Website: https://www.niddkrepository.org/niddk/home.do.

Possible research topics for DPT-1 serum samples include, but are not limited to:

• Analysis of serum for new biomarkers (metabolomic, proteomic, etc.) associated with parenteral or oral treatment with insulin in the DPT-1 trial, with the goal to better understand the effects of treatment on autoimmune responses.
• Analysis of serum for new biomarkers (metabolomic, proteomic, etc.) associated with diabetes risk progression, disease protection, or progression to disease (such as conversion from single to multiple autoantibody status, or from normal to abnormal (pre-diabetic) glucose tolerance), or samples from subjects with risk who were extensively followed with no disease progression.

5. The Type 1 Diabetes TrialNet is an international network of investigators, clinical centers, and core support facilities that recruits patients and 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 Natural History Study enhances understanding of how the disease develops in individuals at risk and thus helps in the formulation of future trials. The Natural History study provides the basis for risk assessment and recruitment of at-risk subjects into clinical trials aimed at preventing the disease in susceptible individuals, see weblink for publications from TrialNet: (http://www.diabetestrialnet.org/publications/publications.htm). TrialNet samples available under this FOA are described below. Applicants must apply for access to samples using ancillary studies application procedures: http://www.diabetestrialnet.org/ancillary/ See also TrialNet policies for access to samples from the archive: http://www.diabetestrialnet.org/documents/ancillary/1ANSARCHIVEACCESSANCILLARYPOLICYfinal.pdf

a) The TrialNet Natural History Study collects serum, RNA, plasma, and PBMC every 6 months from enrolled subjects at risk for disease, and a smaller number of control subjects. Samples from selected subjects within the Natural History study will be made available. Check the TrialNet website (link above) for specific information about the available collection, and for instructions on how to apply for access.

• Scientific questions that can be addressed using this collection include some of those described above for the DPT-1 collection, but in addition allow explorations of cellular functional phenoptypes since living cells were collected (see TrialNet website for details).

b) The TrialNet Mycophenolate Mofetil-Daclizumab (MMF/DZB) clinical trial tested whether two immunosuppressive drugs used in combination, MMF and DZB, could stop the ongoing destruction of beta cells in new onset type 1diabetes patients, relative to MMF alone or placebo control. The clinical trial was stopped early when it became clear that the drugs were not able to stop the decline in C-peptide production (Diabetes Care. 2010 Apr;33(4):826-32.). Samples that potential collaborators may apply for include PBMC, whole blood RNA, and serum. Check the TrialNet website for specific information about the available collection, (samples may be limited), and for instructions on how to apply for access.

Possible research topics include, but are not limited to:

• investigations of correlates of disease progression after diagnosis,
• biomarkers that may have been altered by drug treatment, yet did not impact the disease process sufficiently to delay or prevent C-peptide decline.

c) The TrialNet Anti-CD20 trial tested the effects of the drug rituximab (anti-CD20) on progression of type 1 diabetes in new onset patients. This randomized, double-blind study used rituximab to deplete B cells and tracked the decline in C-peptide over 2 years (primary endpoint at 1 year). The study showed a statistically significant maintenance of C-peptide production at 1 year in type 1 diabetes patients that received the active drug compared to placebo (N Engl J Med. 2009 Nov 26;361(22):2143-52.), although the effect waned at the two years. Samples that potential collaborators may apply for includes serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, (samples may be limited), and for instructions on how to apply for access.

Possible research topics include, but are not limited to:

• investigations of correlates of response to rituximab (i.e., B cell depletion and recovery, C-peptide preservation), as well as biomarkers that may be affected by drug treatment and yet did not impact C-peptide preservation.
• In the rituximab study, some subjects in the drug-treated group were seen to preserve their C-peptide production better than others. Assays that could predict or explain the responder/non-responder phenotype could be valuable for understanding the trial and designing more effective interventions.

d) The TrialNet CTLA-4-Ig trial tested the effects of the agent "abatacept" (CTLA-4-Ig, Orencia) on progression of type 1 diabetes in new onset patients. Abatacept interferes with the activation of T cells by binding to the molecules CD80/86 (expressed on antigen presenting cells) and blocking their interaction with the co-stimulatory receptor CD28 (expressed on T cells). This double-blinded, placebo control trial showed that abatacept, given monthly, delayed the decline of C-peptide (a measure of beta cell function) relative to placebo controls (Lancet. 2011 Jun 28). Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.

Possible research topics include, but are not limited to:

• investigations of correlates of response to abatacept (i.e., C-peptide preservation, or measures of co-stimulatory blockade), as well as biomarkers that may be affected by drug treatment and that did or did not correlate with C-peptide preservation in individual subjects.

e) The TrialNet GAD-alum trial (randomized, blinded, and placebo controlled) tested whether 2 or 3 spaced vaccinations using GAD protein in alum, relative to alum alone, could delay C-peptide decline in new onset subjects . GAD-alum was predicted to modulate the antigen-specific immune response to GAD antigen, through either response type skewing or induced regulation, and to thereby interfere with pathogenesis. The study showed no difference between either of the active drug dosing arms, and the placebo, in the primary or secondary outcome measures at 12 months (Lancet. 2011 Jun 28). Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.

Possible research topics include, but are not limited to:

• investigations of correlates of response to GAD, (i.e, immune responses to GAD), as well as biomarkers that may be affected by drug treatment and that did or did not correlate with C-peptide changes in individual subjects.

f) The TrialNet Anti-IL-1 beta (canakinumab trial) showed that inhibition of the IL-1 inflammatory pathway could not delay the decline of C-peptide in new onset T1D patients at 1 year. Samples that potential collaborators may apply for include serum, plasma, PBMC and whole blood RNA. Check the TrialNet website for specific information about the available collection, and for instructions on how to apply for access.

Possible research topics include, but are not limited to:

• investigations of correlates of response to canakinumab (i.e., measures of inflammation), as well as biomarkers that may be affected by drug treatment and that did or did not correlate with C-peptide changes in individual subjects.

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 Resubmissions of PAR-11-350 The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NIDDK intends to fund up to an estimate of $5,000,000 contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	The award project period shall not exceed 3 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.

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)

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.

Applicant organizations must complete the following registrations as described in the SF424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• Grants.gov
• eRA Commons

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

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

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.

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

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

1. To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

2. Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

3. Of an application with a changed grant activity code.

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.

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.

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

The letter of intent should be sent to:

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: [email protected]

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

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

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

Research Strategy

• Background and rationale for request of these limited, irreplaceable, and valuable clinical samples is required. The question being posed by the investigator must be appropriate to the source of the biospecimens, how they were collected, prepared, analyzed, and stored, their age, and the phenotypic and other accompanying data. Include detailed information about which samples are requested (use the available data to specify samples characteristics). If you will be combining the results from the proposed study with those obtained from other samples, be sure to explain how the additional samples will fit in with your overall study design. Funding for analysis of additional samples from other studies is allowed if it is well-justified and important for understanding the specific clinical studies listed below.
• Specific objectives, including how the results would be integrated with other study results, and the impact of the results on understanding disease progression or response to treatment should be described.
• The application must include assay details and methodology, including amounts and type of samples (applicants should request the minimum volume required for their assay), assay variability and quality control, expected effect sizes and group differences, a statistical plan with calculations to show that the available and requested samples should be sufficient to answer the question. 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.

Letters of Support

Documentation from the relevant clinical consortia confirming that access to samples has been approved, or documentation from the NIDDK Repository that requested samples are available, should be included as a Letter of Support.

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.

Appendix

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

Foreign (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.

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

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

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.

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 (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. 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 [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

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

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

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

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?

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?

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

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

For resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not applicable

Revisions

Not applicable

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

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), 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. Following initial peer review, recommended applications will receive a second level of review by the 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.

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.

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.

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

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.

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

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

For TrialNet and DPT-1:

Lisa M. Spain, Ph. D.,
Program Director for Immunobiology of Autoimmune Endocrine Diseases

Division of Diabetes, Endocrinology, and Metabolism
National Institute of Diabetes Digestive & Kidney Diseases (NIDDK)
Telephone: 301-451-9871
Email:[email protected]

For DCCT/EDIC:

Teresa L. Z. Jones, MD
Program Director for Diabetic Complications
Division of Diabetes, Endocrinology, and Metabolism
National Institute of Diabetes Digestive & Kidney Diseases (NIDDK)
Telephone: 301 435-2996
Email: [email protected]

For GoKIND:

Rebekah Rasooly, Ph. D.
Program Director
Division of Kidney, Urologic, & Hematologic Diseases (NIDDK)
Tel: 301-594-6007
Fax: 301-480-3510
Email: [email protected]

Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: (301) 594-8897
FAX: (301) 480-3505
Email: [email protected]

Diana O'Donovan
Senior Grants Management Specialist
Grants Management Branch, NIDDK
Telephone: 301-594-8868
Fax: 301-594-9523
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.