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
Type 1 Diabetes TrialNet Clinical Network Hub (U01 Clinical Trial Not Allowed)
Activity Code
U01 Research Project – Cooperative Agreements
Announcement Type

Reissue of RFA-DK-13-009

Related Notices
None
Funding Opportunity Announcement (FOA) Number
RFA-DK-18-008
Companion Funding Opportunity
RFA-DK-18-509, U01 Research Project – Cooperative Agreements
Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847

Funding Opportunity Purpose

This FOA invites applications to fund continuation of the Type 1 Diabetes TrialNet Clinical Network Hub (HUB), a screening and clinical activities coordination unit. The main objective of the HUB is to develop creative approaches to screening, recruitment, and trial implementation, and to increase the operational efficiency and flexibility of the TrialNet network.

Key Dates

Posted Date

January 10, 2019

Open Date (Earliest Submission Date)
February 21, 2019
Letter of Intent Due Date(s)

February 21, 2019

Application Due Date(s)

March 21, 2019 by 5:00 PM local time of applicant organization.

All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

 

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

June/July 2019

Advisory Council Review

October 2019

Earliest Start Date

December 2019

Expiration Date
March 22, 2019
Due Dates for E.O. 12372
Not Applicable
Required Application Instructions
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

 

The TrialNet Clinical Network Hub (HUB) serves as a TrialNet coordination unit for screening and clinical activities and works to increase the efficiency of risk screening, develop new and creative approaches to screening, recruitment of subjects, and implementation of trials. The HUB increases the operational efficiency and flexibility of the TrialNet network.

 

The HUB’s major functions will include, but are not limited to:

HUB Activities to Enhance Risk Screening and Prevention Trial Recruitment :

The HUB is responsible for developing and leading a coordinated program to enhance risk screening, recruitment and retention for TrialNet prevention trials. 

Currently, the productivity of TrialNet Clinical Centers and Affiliate Sites varies. The goal is to maximize opportunities for risk screening that lead to active participation in prevention trials. This is expected to be accomplished using a number of strategies, including but not limited to supporting novel approaches and enhancing successful approaches to screening outreach. This will include a coordinated effort to interact with T1D families, diabetes care providers, diabetes self-care supply providers, and voluntary disease research and support organizations (such as JDRF, Helmsley Trust, ADA, Children With Diabetes, etc).

HUB Activities to Support Clinical Trials and Ancillary Studies :

During the planning phase of approved TrialNet trials and Living Biobank Ancillary Studies, the HUB is responsible for: (1) working with TrialNet investigators, outside partners as needed, and the TNCC to finalize protocols and consent forms; (2) providing input to the TNCC on case report forms (CRFs); (3) participating in site selection and activation as needed; (4) working with the TNCC to provide a subject recruitment plan; (4) working with Living Biobank ancillary study project investigators to determine the feasibility of their project as well as alignment with TrialNet's mission; and (5) monitoring the IRB approval process and promoting rapid approval through well-developed and complete documentation at initial submission and through rapid and comprehensive responses to IRB comments and concerns.

During the trial implementation phase, the HUB is responsible for: (1) coordinating screening and recruitment efforts across the network; (2) coordinating clinical team visits to provide help with interventions at sites as needed; (3) overseeing, in collaboration with the TNCC, enrollment and retention, and developing outreach interventions to help clinical sites succeed; (4) working with the TNCC Clinical Monitoring Group as well as the clinical sites to ensure appropriate protocol implementation and adherence to protocols; and (5) conducting site visits as needed.

During the trial data analysis and publication phase, the HUB is responsible for: (1) assisting the TNCC and clinical sites in finalizing IRB reports; (2) working with the TrialNet Executive Committee to coordinate the communication of trial results to the investigators, patients and public; and (3) working with the TNCC and network investigators in the publication of the primary and, if applicable, secondary manuscripts.

The HUB should also explore options to engage a broader set of investigators external to the immediate study group to provide opportunities to analyze the data and participate in parent studies by means of ancillary studies, along with opportunities for local analyses by study investigators and other qualified researchers at their institutions to support disseminated data analyses.

HUB Activities to Enhance Clinical Administration :

TrialNet recently transitioned to a central IRB for all U.S. clinical sites. The HUB will coordinate and manage TrialNet central IRB communication and documentation, including but not limited to: (1) tracking approvals; (2) maintaining regulatory documents; and (3) communicating with local IRBs.

The HUB will oversee clinical aspects related to the development and implementation of TrialNet's multi-center clinical projects over the funding period. The HUB will oversee clinical implementation of prevention and new onset trials and will provide clinical evaluations and recommendations on issues such as publications/presentations, clinical monitoring activities and per-patient per-visit capitated reimbursements to clinical sites.

The HUB PD/PI will participate on the TrialNet Executive Committee and will serve on other network working groups. The HUB will work closely with the TNCC, Clinical Centers and Chair’s Office in a collaborative and interactive manner. 

The HUB will submit a scope of work document that details its TrialNet tasks and responsibilities. It is essential that the tasks required in planning and executing a complex, multi-centered trial be clearly defined, and that the responsibilities of the collaborators (including HUB, TNCC, Chair’s Office and Clinical Centers) be delineated. It is therefore required that the HUB show the ability for excellent and seamless communication and coordination and demonstrate an in-depth understanding of the overall operational conduct of complex, multi-center trials.

 

Objectives and Scope

This FOA invites applications for the TrialNet HUB. A major function of the HUB is to optimize risk screening and enrollment into trials across TrialNet. The HUB budget will include funds for enhancements to optimize consistency, efficiency and productivity across the network. The HUB is expected to effectively manage costs while enhancing productivity. The HUB PD/PI will have a shared leadership role in the existing TrialNet organizatio

 

Background

 

TrialNet was established to provide a large, complex, highly collaborative clinical trials network to develop and implement trials aimed at preventing type 1 diabetes and halting T1D disease progression by preserving insulin production before and after diagnosis.

 

The TrialNet partnership currently consists of 17 North American Clinical Centers (funded by NIDDK U01 cooperative agreements), six international Clinical Centers (infrastructure funded by Juvenile Diabetes Research Foundation [JDRF]), a TrialNet Clinical Network Hub ("HUB") funded by NIDDK cooperative agreement) and a TrialNet Coordinating Center ("TNCC") (funded by NIDDK cooperative agreement). The HUB optimizes network approaches to screening, recruitment, and trial implementation, and increases operational efficiency and flexibility of the TrialNet network. The TNCC provides the network with scientific leadership in study design and monitoring, and oversees data processing, biostatistical analyses and administrative operations. In addition, going forward, the TNCC (funded by NIDDK cooperative agreement) will select the North American TrialNet Clinical Centers, which will be funded via TNCC subcontracts. The TrialNet Chair office, a subcontractor of the TNCC, provides scientific and medical leadership, oversees protocol/consent/volunteer handbook development, and manages the receipt and review of proposals for future TrialNet studies. In addition, TrialNet has >200 Affiliate Sites. Each Affiliate Site is linked to a Clinical Center, but unlike Clinical Centers, Affiliate Sites do not receive infrastructure support for personnel, space or other ancillary costs. Affiliate Sites screen T1D family members for autoimmunity and eligibility for TrialNet studies. Some Affiliate Sites conduct trials and follow subjects in addition to screening for risk. The TrialNet network is supported by approximately 20 central laboratories and support units (all TNCC subcontractors).

 

TrialNet's study of the pathogenesis of T1D in individuals with early, non-symptomatic stages of disease led to establishment of the three distinct stages of T1D. This model of T1D development has been endorsed by the JDRF, ADA and Endocrine Society. The first two stages of T1D, identifiable by TrialNet screening prior to onset of T1D symptoms, are Stage 1, =2 positive diabetes-related autoantibodies, and Stage 2, =2 positive diabetes-related autoantibodies plus impaired glucose tolerance. Stage 3 is reached when there is a clinical diagnosis of T1D. Identifying T1D in its earliest stage allows for prompt intervention and the potential to alter the disease course. Thus, TrialNet's goal is to identify T1D in its earliest stage to stop disease progression by preserving ß-cell production.


A number of TrialNet studies have been developed, implemented, and/or completed:

TrialNet Studies

Title

Enrollment

Launch

Completion

Effects of Oral Insulin in Relatives of Individuals with T1D in the Diabetes Prevention Trial-Type 1

Target: 372

Final: 372

1994

2003

Improving Metabolic Assessments in T1D Clinical Trials –Comparison of the Reliability of Mixed Meal Tolerance Test and Glucagon Stimulation Test

  Target: 120

Final: 148

2004

2005

Comparative Study Between the Cytokine, ELIspot, Tetramer, Immunoblot and T Cell Proliferation Assays Using Fresh Blood Samples from Subjects with Recent Onset T1D

Target: 60-100

Final: 96

2005

2007

“Pathway to Prevention” Natural History Study of the Development of T1D (Phase 1 – Screening, Phase 2/3 – Enrollment)

The primary purpose of TrialNet screening is to identify potential subjects for prevention trials, but also to generate data on contributors of disease risk, and provide samples for mechanistic studies.

Ongoing

To date screening: 191,432

To date at risk:

6,444

2004

Ongoing

New Onset T1D – Mycophenolate Mofetil/Daclizumab Clinical Trial

Target: 120

Final: 126

2004

Enrollment: 2007

Outcome: 2009

Effects of Rituximab on the Progression of T1D in New Onset Subjects

Target: 66

Final: 87

2006

Enrollment: 2007

Outcome: 2008

Oral Insulin for Prevention of Diabetes in Relatives At Risk for T1D

Testing prediction from DPT-1 Oral Trial

Target: N/A*

Final:

391 (1° stratum)

562 (all strata)

2007

Enrollment: 2015

Outcome: 2017

Nutritional Intervention to Prevent T1D – Pilot Trial

Target: 90

To Date: 123

2006

Enrollment: 2008

Outcome: 2009

Effects of CTLA-4 Ig (Abatacept) on the Progression of T1D in New Onset Subjects

Target: 108

Final: 112

2008

Enrollment: 2009

Outcome: 2011

Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of T1D in New Onset Subjects

Target: 126

Final: 146

2008

Enrollment: 2009

Outcome: 2011

Effect of Metabolic Control at Onset of Diabetes on Progression of T1D**

Target: 72

Final: 71

2009

Enrollment: 2011

Outcome: 2012

Effects of Canakinumab on the Progression of Type 1 Diabetes in New Onset Subjects

Target:  66

Final: 71

2010

Enrollment: 2011

Outcome: 2012

Anti-CD3 (Teplizumab) for Prevention of Diabetes in Relatives At Risk for T1D

Target: N/A*

To Date: 76

2011

Enrollment: 2016

Outcome: 2018

Long-Term Investigative Follow-Up Trial (LIFT)

Target: TBD

2012

Ongoing

Effects of CTLA-4 Ig (Abatacept) for Prevention of Glucose Intolerance in Relatives at Risk for T1D

Target: 108

To Date: 161

2013

Enrollment: 2019

Outcome: 2021

Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset T1D

Target: 84

Enrolled: 89

2015

Enrollment: 2016

Outcome: 2017

Exploring Immune Effects of Oral Insulin in Relatives at Risk for T1D

Target: =40

Enrolled: 92

2016

Enrollment: 2017

Outcome: 2017

Methyldopa for Reduction of DQ8 Antigen Presentation in Subjects at Risk for T1D

Target: 36

Enrolled: 0

2018

Enrollment: 2019

Outcome: 2020

Hydroxychloroquine for Prevention of Abnormal Glucose Tolerance and Diabetes in Individuals At-Risk for T1D

Target: 201

Enrolled: 0

2018

Enrollment: 2022

Outcome: 2023

Rituximab and Abatacept for Prevention of Diabetes in Individuals At-Risk for T1D

Target: 36

Enrolled: 0

2018

Enrollment: 2020

Outcome: 2022

*Study uses a maximum information design so there is not an exact enrollment target. Enrollment will be complete when the necessary number of events occurs.

**Trial performed jointly with DirecNet at TrialNet Centers.

***Immune Tolerance Network (ITN) studies reviewed and approved by TrialNet and conducted at TrialNet Centers include: 1) Treatment of Recent Onset T1D with AntiCD3 Monoclonal Antibody; 2) Thymoglobulin for New Onset T1D; 3) A Phase I Trial of Proleukin and Rapamune in Recent Onset T1D; and 4) Treatment of Recent Onset T1D with Anti-IL6R (Tocilizumab)

 

TrialNet’s primary objective is to delay or prevent the development of T1D in persons at risk. Large numbers of relatives must be screened to identify those with at least moderate risk (~35% over 5 years) of clinical disease. The goal of TrialNet is to test safe and potentially effective interventions aimed at disease prevention in individuals at risk.

 

In addition to prevention trials, TrialNet tests interventions aimed at decreasing ß-cell destruction and/or enhancing ß-cell survival in patients newly diagnosed with T1D. This goal is approached through independent studies as well as collaborations with partners, such as the Immune Tolerance Network (ITN; NIAID funded) and the pharmaceutical industry. Long-term studies have demonstrated that the longer patients with T1D maintain ß-cell function, as measured by stimulated C-peptide production, the better protected they are from serious diabetes complications (DCCT/EDIC). Thus, it is anticipated that intervention studies in the new-onset T1D population could provide clinical benefits to participants as well as identify agents with potential efficacy for T1D prevention. With a T1D incidence of 30,000 persons per year in the United States, the pool of subjects eligible for new onset trials is relatively small and is further limited by age restrictions and a requirement for enrollment within weeks after diagnosis. The TrialNet HUB plays a vital role in providing Clinical Centers with support to accomplish effective recruiting and to conduct and follow subjects enrolled into trials. TrialNet prevention trials also benefit from TrialNet's participation in new onset trials. Family members of individuals enrolling in new-onset T1D treatment trials are often interested in being screened for T1D risk as well as prevention trial participation. In addition, TrialNet strives to leverage ongoing clinical studies to generate information to improve understanding of the pathophysiology of T1D, facilitating the identification of biomarkers to serve as intermediate study endpoints. This enables intervention earlier in the disease process as well as decreasing trial duration and sample size. This can be accomplished through separately funded ancillary studies (such as "living biobank" FOAs) utilizing TrialNet subjects or through provision of biosamples to independent investigators and/or consortia with complementary goals (such as Human Islet Research Network [HIRN]).

 

Purpose

There is a large resource cost in screening people for T1D risk and in treating and following subjects to disease onset, often for five or more years. Since T1D is a relatively rare disease, there is a need for a large and geographically distributed screening effort. Screening involves the identification of children and young adults who have relatives with T1D, obtaining their blood samples, and determining their T1D risk by measurement of diabetes-related autoantibodies. The autoantibody positivity rate for this population of relatives is only 3-5%. Those with positive autoantibodies are further staged for risk using metabolic and genetic tests. Increased screening and recruitment rates, along with optimal efficiency in the screening process, improve trial feasibility, enabling TrialNet to reach its goal of T1D prevention.

 

In addition to prevention trials, TrialNet also conducts trials in newly-diagnosed subjects independently and in partnership with other NIH funded networks or grantees, industry, foundations, or academia. For example, TrialNet Clinical Centers actively participate in the recruitment and conduct of trials in partnership with the ITN. These partnerships expand TrialNet's capacity to test new agents that could be useful for disease prevention and to further contribute to research on strategies for disease intervention later in disease progression.

 

This next phase of TrialNet involves recompetition of the HUB (this FOA) and TNCC (under a separate FOA). The HUB will serve as a coordination unit for screening and clinical activities and will work to increase the efficiency of risk screening, develop new and creative approaches to screening, recruitment, and trial implementation, and increase the operational efficiency and flexibility of the TrialNet network. The TNCC will be responsible for providing the network with scientific leadership in study design and monitoring, and will oversee data processing, biostatistical analyses and administrative operations. The TNCC will select and fund (via subcontracts) the TrialNet Clinical Centers, which were previously funded by individual cooperative agreements. The TNCC will also fund (via subcontracts) the TrialNet Chair Office and TrialNet central laboratories and support units. In addition to supporting TrialNet Clinical Center infrastructure, the TNCC will provide capitated payments, based on TrialNet-related activities, to Clinical Centers and Affiliate Sites.

 

Network Projects

Over the project period, TrialNet will continue its ongoing prevention and new-onset trials. In addition, the network will plan and prioritize new prevention and new-onset trials to replace ongoing trials, as needed, and will offer opportunities to participate in research to subjects not currently eligible for ongoing trials. TrialNet will also continue to participate as a partner with separately funded industry-, foundation- and NIH-sponsored new-onset trials. The exact number of protocols supported during the project period will depend on the nature and extent of the investigations proposed and the availability of funds. In addition, the network will continue to perform mechanistic studies in conjunction with trials as well as provide access to samples from and subjects in TrialNet clinical studies. This will generate information to improve understanding of the pathophysiology of T1D and to identify biomarkers to serve as intermediate study endpoints, enabling intervention earlier in the disease process and shorter trials using fewer subjects.

 

Jointly, the TrialNet HUB and TrialNet TNCC are expected to optimize TrialNet’s decision-making process, efficiency and productivity. Details about trial selection and network governance are presented below.

 

The NIDDK Technology Advancement Office must be consulted early in the process when an NIDDK-funded study enters into a collaboration agreement and the NIDDK Regulatory Specialist consulted early in the process when a protocol may be required to operate under an IND/IDE. These consults will be facilitated by the NIDDK Program Official. 

 

TrialNet Organization 

Open competition of the TrialNet HUB is being conducted concurrently with a limited competition for the TNCC through a separate FOA (RFA-DK-18-509). The TNCC will select the North American TrialNet Clinical Centers, which will be funded via subcontracts. Applicants to this HUB funding opportunity are strongly encouraged to contact the NIH Program Official listed below before preparing an application. In addition, NIH staff will lead webinars to describe and answer questions about this opportunity and TrialNet. 

 

Clinical Center PDs/PIs will serve as members of the TrialNet Steering Committee (SC) and as a group will comprise the majority of the SC. Steering Committee voting members include the Clinical Center PDs/PIs, the TNCC PD/PI, the HUB PD/PI and the NIDDK Project Scientist. TrialNet also has a Collaborative Mechanistic Studies Panel (CMSP), a group of T1D and immunology experts (including Clinical Center PDs/PIs and external consultants) who interact with the research community to provide guidance on TrialNet mechanistic studies and enhance biomarker discovery in the context of TrialNet's mission.

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New
Renewal

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

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $1,000,000 in FY 2019 to fund 1 award. It is expected that one award will be made, contingent upon NIH appropriations and the submission of one or more meritorious applications.

Award Budget

Application budget is limited to approximately $650,000 in direct costs. Awards for all years may vary based on available funds and network activity. Budget for all years must reflect the actual needs of the proposed project?.

 

 

Award Project Period

The maximum project period is 5 years. 

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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
Foreign Institutions

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

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

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

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – 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.
  • 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.

3. Additional Information on Eligibility

 

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

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)

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) 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 letter of intent should be sent to:

John Connaughton, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: NIDDKLetterofIntent@mail.nih.gov

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

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

R&R Subaward Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Cover Page Supplement
All instructions in the SF424 (R&R) Application Guide must be followed.
PHS 398 Research Plan
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

 

Specific Aims : Applicants should list and describe the specific aims of the HUB, focusing on the overall research agenda and strategic plan. Applicants should briefly describe their plans for a coordinated program to enhance risk screening and recruitment for TrialNet’s prevention and new-onset trials, as well as improvements in coordination of TrialNet's clinical activities.

 

Research Strategy : The application should address the following functions in subsections as described below.

 

HUB Activities to Enhance Risk Screening and Prevention Trial Recruitment

  • Background: Applicants should provide a description of: (1) the challenges that limit effective screening and trial recruitment for T1D prevention trials; and (2) opportunities to build on the success of TrialNet and other networks to increase screening and trial recruitment efficiency. A data driven approach is strongly encouraged, including an evaluation of patient populations and information about patient acceptance of prevention trials. Applicants are encouraged to provide examples and describe features of recruitment strategies they have utilized.
     
  • Innovation: Applicants should describe any innovations in approach to reach out to T1D communities for screening and recruitment, and to increase cost efficiency and productivity across the network.
     
  • Approach: Applicants should describe their approach to and specific plans for accomplishing increased screening and trial enrollment network-wide, including plans for supporting Affiliate Sites. Applicants should describe, in detail, their experience addressing challenges related to recruiting, screening and enrollment for trials, focusing on individuals at risk for the development of type 1 diabetes.
     

HUB Activities to Support Clinical Trials

  • Background: Applicants should describe their experience, as well as current challenges and opportunities, with each phase of T1D protocol development and implementation, site selection and evaluation, and history in developing recruitment plans.
     
  • Innovation: Applicants should describe innovations in their approach to enhance the quality and efficiency of trial conduct through the phases of planning, implementation and publication.
     
  • Approach: Applicants should describe their specific approach for accomplishing network coordination and utilization of a central IRB to accelerate the timeline for trial launch, facilitating trial protocol development and implementation, and promoting rapid and effective reporting and publication of results. Applicants should also describe their approach to optimizing subject retention in type 1 diabetes clinical trials. Applicants are strongly encouraged to assemble an experienced research team, and to list additional clinical research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution.
     

HUB Activities to Enhance Clinical Administration

  • Background: The PD/PI(s) for the HUB will be physician(s) and clinical trialist(s) with a track record in recruiting and enrolling subjects for multi-center clinical trials in T1D prevention. Applicants should describe their experience and capabilities, as well as the challenges and opportunities inherent in the clinical oversight of a large clinical trials network such as TrialNet. Applicants should document and describe their role as a collaborative leader in recent multi-center trials in T1D without duplicating information in the biosketches .
     
  • Innovation: Applicants should describe innovations in their approach to collaborative and interactive communication across the TrialNet network, especially from the clinical point of view, including interactions with Clinical Center and Affiliate Site staff to enhance TrialNet operations.
     
  • Approach: Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the Clinical Centers, the TNCC and the NIDDK and its partners (both academic and industry). Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., experience in clinical trial collaborations with industry partners, NIH-funded clinical trial groups and other NIH consortia). Applicants should indicate how potential network colleagues (from academia or industry) will be motivated to work with TrialNet, supported in the conception phase, and integrated into the network in the planning and implementation phases. Since TrialNet presents a rich environment for early stage investigators to be exposed to and to develop additional research skills, and to assist them in progressing to more senior status, applicants should describe their plans to reach out to young investigators.


Letter of Support: Institutions will be required to document commitment to the PD(s)/PI(s) by providing departmental and institutional support letters. In addition, applicants are encouraged to demonstrate support via other means (e.g., additional protected time, departmental research leadership position, facilities, space, or resources for the PD(s)/PI(s)).

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

The following modifications also apply:

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

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information
When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed.
PHS Assignment Request Form
All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research
 

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies.  CDEs are data elements that have been identified and defined for use in multiple data sets across different studies.  Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.  NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository).  NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection.  The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.  Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects. 

 

Post Submission Materials
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted in support of the NIH mission 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.

 

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?

 

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

Specific to this FOA:

  • Does the PD/PI provide evidence for consistent collaborative leadership in recent multi-center trials in T1D prevention, and evidence of experience in and willingness to participate in a collaborative program as described in this FOA?
  • Does the PD/PI have experience in screening and recruiting for T1D prevention trials?
  • Does the PD/PI describe their experience, as well as current challenges and opportunities, with each phase of T1D protocol development and implementation, site selection and evaluation, and history in developing recruitment plans?
  • Does the PD/PI describe their experience and capabilities, as well as the challenges and opportunities inherent in the clinical oversight of a large clinical trials network such as TrialNet?
  • Does the PD/PI propose an experienced research team, and list additional clinical research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution?
  • Does the PD/PI describe their plans to reach out to young investigators?

 

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?

Specific to this FOA: Does the PD/PI describe innovations in approach to reach out to T1D communities for screening and recruitment, to increase cost efficiency and productivity across the network, and to enhance the quality and efficiency of trial conduct through the phases of planning, implementation and publications? Does the PD/PI describe innovations in their approach to collaborative and interactive communication across the TrialNet network, especially from the clinical point of view, including interactions with Clinical Center and Affiliate Site staff to enhance TrialNet operations? Does the PD/PI d?e?s?c?r?i?b?e? a data-driven approach to support their oversight plans in their application, including an evaluation of patient populations and information about patient acceptance of prevention trials?

 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the  proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA: Does the PD/PI describe their approach to and specific plans for accomplishing increased screening and trial enrollment network-wide, including experience addressing challenges related to recruiting, screening and enrollment for trials and plans for supporting Affiliate Sites? ?Does the PD/PI provide examples and describe features of recruitment and subject retention strategies that they have successfully utilized in the past? Does the PD/PI describe opportunities to build on the success of TrialNet and other networks to increase screening and trial recruitment efficiency? Does the PD/PI describe their specific approach for accomplishing network coordination and utilization of a central IRB to accelerate the timeline for trial launch, facilitating trial protocol development and implementation, and promoting rapid and effective reporting and publication of results? Does the PD/PI describe any special expertise or unique strengths they can offer to the collaborative research effort, and their willingness to participate in a collaborative and interactive manner with the Clinical Centers, the TNCC and the NIDDK and its partners (both academic and industry)?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

 

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

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.

 

For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

 

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

 

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

 

Not Applicable

 

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

 

Not Applicable

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.

 

Not Applicable

 

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

 

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

 

 

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

 

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.

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

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

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

2. Administrative and National Policy Requirements

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

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

The PD(s)/PI(s) will contribute to and support the following activities:

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

11. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the archiving and storage of data and biosamples collected in large, multi-site studies funded by NIDDK. The PI or his/her designee will support the TNCC in coordination with the NIDDK Data Repository to prepare the collected data for eventual archiving and distribution. In addition, if applicable, the PI or his/her designee will assist the TNCC in its work with the NIDDK Biosample Repository to coordinate procedures for coding, shipping, processing, receipt, and storage of study samples that are to be maintained in the Repository. All samples and data transferred to the Repositories will be under the custodianship of the NIDDK, although the study’s Steering Committee will have proprietary control of and exclusive access to the samples and data for an agreed-upon period of time. Subsequently samples and data will be available to the wider scientific community in accordance with the NIH policy on Data Sharing ( http://grants.nih.gov/grants/policy/data_sharing/ and,

http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals, and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm), as well as the NIDDK policy for data sharing in multi-center and large single-center clinical studies http://www.niddk.nih.gov/research-funding/process/human-subjects-research/Documents/PublicversionNIDDKdatasharingpolicy2013July2013.pdf.

 

12. The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the HUB PD(s)/PI(s) will assist the sponsor or his/her designee to perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors ( http://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html).

 

13. Agree that any third-party (including both industry and academia) collaboration should be governed by a research collaboration agreement (e.g. Clinical Trial Agreement, Research Collaborative Agreement, Memorandum of Understanding, etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures. The NIDDK Program Official may consult with others at NIH including the NIDDK Technology Advancement Office.

 

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

 

An NIDDK Project Scientist with substantial involvement will:

  1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Project Coordinator, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.
  2.   For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or Project Coordinator will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.
  3.   Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.
  4.   Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:

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

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

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

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

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

  1. Interact with the Program Director(s)/Principal Investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the Program Director/Principal Investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
     
  2. Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.
     
  3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
     
  4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
     
  5. Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:
 
In addition to the interactions defined above, NIDDK Project Scientist and Awardees shall share responsibility for the following activities:
 
Steering Committee.
 
A Steering Committee organized by the study investigator(s) will be the main governing body of the study.
 
The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official and will provide periodic supplementary reports upon request.
 
The Steering Committee will be composed of all Program Director(s)/Principal Investigator(s), (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.
 
A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK, in consultation with the Steering Committee. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK and by interacting closely with the awardees during protocol development and implementation.

Dispute Resolution

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

 

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Application Submission Contacts
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

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

Peer Review Contact(s)

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

 

Financial/Grants Management Contact(s)

Natasha Loveless
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8853
Email: Natasha.Loveless@nih.gov

 

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Authority and Regulations
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
This FOA is supported under the authority of P.L. 115-123, Bipartisan Budget Act of 2018; Section 50902. Extension for special diabetes programs.


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