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 Centers (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissuance of RFA-DK-08-011

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.
  • August 14, 2013 - See Notice NOT-DK-13-017. Notice of Availability of Webinar Questions and Answers.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

RFA-DK-13-010

Companion Funding Opportunity

RFA-DK-13-009, U01 Research Project – Cooperative Agreements  

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.847 

Funding Opportunity Purpose

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the delay or prevention of type 1 diabetes (T1D).  This opportunity will provide infrastructure support for TrialNet Clinical Centers, allowing them to recruit, treat, and follow subjects in TrialNet studies and trials.  In addition, funding will be provided for Clinical Centers to support Affiliate Sites.  In addition to this opportunity, a separate, new TrialNet unit is planned, the Clinical Network Hub (CNH).  The CNH will focus on the coordination and enhancement of screening and recruiting activities.

Key Dates
Posted Date

June 18, 2013

Open Date (Earliest Submission Date)

October 27, 2013

Letter of Intent Due Date(s)

October 27, 2013

Application Due Date(s)

November 27, 2013, by 5:00 PM local time of applicant organization.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March/April 2014

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

November 28, 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.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Background

The Diabetes Prevention Trial-Type 1 (DPT-1, initiated in 1993) tested whether two separate interventions involving insulin administration could prevent progression from autoimmunity to T1D: (1) parenteral insulin in subjects with projected 5-year T1D risk of greater than 50%, and (2) oral insulin in subjects with projected 5-year T1D risk of 25-50%.  Although protective effects of insulin were not demonstrated, DPT-1 did show, in a very large cohort, that: (1) the diabetes risk (over 5-10 years) of relatives of people with T1D could be accurately predicted based on genetic evaluation, tests of autoantibodies in blood, and metabolic status; and (2) trials requiring massive screening efforts to identify eligible subjects and involving intensive treatment regimens could be efficiently accomplished. 

TrialNet, which evolved from DPT-1, was established in 2001 to provide a large, complex, highly collaborative clinical trials network.  The TrialNet partnership currently consists of 14 North American Clinical Centers (funded by NIDDK U01 grants), four international Clinical Centers (infrastructure funded by Juvenile Diabetes Research Foundation [JDRF]), and a Data Coordinating Center (TNCC) (funded by NIDDK contract and grants).  The TNCC provides scientific leadership in study design and monitoring, and performs data processing, biostatistical analyses, and administrative operations.  The TrialNet Chair and Vice Chair offices, subcontractors of the TNCC, provide scientific and clinical leadership, including protocol/consent/volunteer handbook development and oversight of the receipt and review of proposals for future TrialNet studies.  In addition, TrialNet has 220 Affiliate Sites.  Affiliates are supported by regional Clinical Centers and screen T1D family members for autoimmunity and eligibility for TrialNet studies.  In addition, some Affiliate Sites conduct trials and follow subjects.  The Network is supported by 20 central laboratories and support units (all TNCC subcontractors).

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

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 (Screening, Follow-Up of At-Risk)

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

Ongoing

To date screening: 114,879

To date at risk:

3,334

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*

To Date:

240 (1° stratum)

350 (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: 26

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 Tolerance in Relatives at Risk for T1D

Target: 206

To Date: 4

2013

Enrollment: 2017

Outcome: 2019

Trichuris suis Ova (TSO) To Prevent Epitope Spreading In People At Risk For T1D

Target: TBD

2013

TBD

*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; and 3) A Phase I Trial of Proleukin and Rapamune in Recent Onset T1D.

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 (~35% over 5 years) risk of clinical disease.  The goal of TrialNet is to test safe and potentially effective interventions aimed at disease prevention to all subjects with moderate to high risk.

In addition to prevention trials, TrialNet’s goal is to test interventions aimed at decreasing ß-cell destruction and/or enhancing ß-cell survival in persons with T1D with residual ß-cell function.   This goal is currently approached through collaboration with partners such as the Immune Tolerance Network (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 this population may also provide clinical benefits to participants.  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 the requirement for enrollment within weeks after diagnosis.  TrialNet plays a vital role in providing supported Clinical Centers to accomplish effective recruiting, conduct and follow-up of treatment trials.  TrialNet's prevention trials also benefit from the network's participation in new onset trials.   Families interested in enrolling their newly-diagnosed family member in a treatment trial will often be interested in screening other family members for potential T1D risk and prevention trial participation. In addition, TrialNet strives to leverage ongoing clinical studies to generate information to improve understanding of the pathophysiology of T1D. This will facilitate the identification of biomarkers to serve as intermediate study endpoints, enabling intervention earlier in the disease process as well as shorter trials using fewer subjects.

This opportunity will fund the infrastructure of TrialNet Clinical Centers to support subject recruitment into trials and studies, trial conduct, subject retention, and follow-up.  Funds will also be provided to Clinical Centers for their staff time and activities in support of Affiliate Sites.  In addition to this opportunity, a separate new TrialNet unit is planned, the Clinical Network Hub (CNH).  The CNH will provide a strong focus on the coordination and enhancement of screening and early recruiting activities, relieving some of this burden from TrialNet's Clinical Centers.  All Clinical Centers and Affiliate Sites will continue to be supported for screening and patient care costs through capitated payments from the TNCC.  These complementary funding announcements will take advantage of an opportunity to restructure TrialNet for greater efficiency of decision making, to increase flexibility of resource allocation, and to better meet the distinct needs of screening as well as clinical trial recruiting and follow-up.

Objectives and Scope

In addition to providing continuing support for highly productive centers, a major goal of this Funding Opportunity Announcement (FOA) is to fill geographical gaps to reduce subject travel burden and increase trial participation across the network. 

It is anticipated that this competition will accommodate Clinical Centers across a range of funding levels and will allow for flexibility for Clinical Centers with changing patient populations.  Clinical Centers need not have or wish to have Affiliate Sites to apply to be a Clinical Center.  Highly productive Clinical Centers are not required to manage an Affiliate Site network to be a Clinical Center.  In addition, some high-performing Affiliate Sites might successfully compete to become an independent Clinical Center and would no longer need network support for their Affiliate Site activities. Other Affiliate Sites might support their own activity through capitated reimbursements with oversight provided by a new TrialNet unit, the Clinical Network Hub (CNH). The CNH will allow TrialNet to more flexibly support current Affiliate Sites or bring up new Affiliate Sites as needed.

Successful Clinical Center applicants will demonstrate the ability to efficiently screen, recruit, treat and follow subjects in T1D prevention trials.  In some cases, individual Clinical Centers in areas of high population density are most effective when they focus on drawing subjects to their Clinical Center for screening and trial participation.  In other cases, Clinical Centers may screen fewer subjects at their own site but effectively reach out to Affiliate Sites and patient populations to provide local and geographically distributed opportunities for trial participation.  Applications that demonstrate active and innovative approaches to improving screening and enhancing trial participation are strongly encouraged.

Clinical Center Program Directors/Principal Investigators (PDs/PIs) will be expected to participate as members of the TrialNet Steering Committee as well as TrialNet’s operational committees (individual trial committees, manuscript committees, clinical operations committees, laboratory monitoring committee, ancillary studies committee, etc). Therefore, Clinical Center PDs/PIs need to demonstrate expertise in type 1 diabetes etiology and pathogenesis as well as their willingness to engage in potentially challenging but scientifically strong interventions and studies that advance the field toward its goal of T1D prevention.

Central Institutional Review Board (IRB)

NIDDK will give preference to Clinical Centers agreeing to use a central IRB of record to accelerate IRB approval in multi-center trials.  To that effect, the network will use a “federated" IRB model.  This model gives participating institutions the option to choose one of three tiers of IRB review: 

Tier 1 indicates reliance on a central IRB as IRB of record; 

Tier 2 indicates designation of a central IRB as IRB of record in addition to involvement of a local IRB;

Tier 3 indicates reliance on a local IRB.

The concurrent review and selection of the Clinical Network Hub will provide an opportunity to coordinate a central IRB of record and manage all required IRB communication and documentation including, but not limited to, tracking approval, maintaining regulatory documents, communicating with local IRBs, and handling adverse event reporting and notifications. 

Budgets and Capitated Payments

Applicants for TrialNet Clinical Center grants will submit budgets based on current and/or planned subject recruitment and follow-up in Pathway to Prevention and other studies, and for support of Affiliate Sites. At least one Coordinator must have no less than 12 person-months devoted exclusively to TrialNet.  Total PD/PI effort must not exceed 3.6 person-months.  Resources for support of Affiliate Sites can be requested by Clinical Centers, as justified, based on specific Affiliate Site support activities described in the application.

Clinical Centers will be offered network-approved fee-for-service reimbursement from the TNCC for the per-subject cost to implement protocols according to rates approved by the Clinical Leadership Committee (CLC) and NIDDK for each protocol. 

After award, funding levels will be re-evaluated yearly based on individual site productivity and available opportunities.  All funded Clinical Centers will be expected to actively participate in all TrialNet studies and trials and to participate, as much as possible, in Living Biobank ancillary studies and partnered new onset trials.   NIDDK will consider geographic distribution of network centers in making awards to ease subject burden and reduce network costs related to travel.

TrialNet Organization 

This recompetition of the TrialNet Clinical Centers occurs at the same time that a new TrialNet unit, the TrialNet Screening Clinical Network Hub, RFA-DK-13-009, will be solicited through a separate competition.  This will require some changes of network functions, organization, and governance.   Applicants to this opportunity and/or the Screening Clinical Network Hub are strongly encouraged to contact the NIH Scientific/Research Contact listed below before preparing an application.  In addition, NIH staff will lead webinars to describe and answer questions about these opportunities and TrialNet.  The dates and times for the webinars are as follows:  July 23 and 26, both at 1:00PM EDT, and August 5 at 3:00PM EDT, and August 8 at 1:00PM EDT. Please contact the Scientific/Research Contact listed below for instructions on how to attend a webinar.

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.  In addition, a Clinical Center Leadership Committee (CLC) will evaluate the feasibility of future clinical trials prior to protocol development and approval.  The CLC will be comprised of up to 7 Clinical Center PDs/PIs (initially selected by NIDDK for 1-3 year terms). Subsequently, membership will rotate with new members selected by Steering Committee vote.

TrialNet will also establish a Strategic Directions Committee (SDC) and a Biomarkers and Mechanisms Panel (BMP).  The BMP will be comprised of T1D and immunology experts (including Clinical Center PDs/PIs and external consultants) who will interact with the research community to enhance biomarker discovery in the context of TrialNet's mission.  The SDC will be made up of representatives from the TNCC, the NIDDK, the Clinical Center PDs/PIs, and the BMP. The SDC will be charged with the development (and yearly update) of a TrialNet Strategic Plan.  This plan will prioritize current and planned trial opportunities for every TrialNet identified risk population to allow a pipeline of new trials and clear direction forward. The plan will be presented to and approved by the Steering Committee yearly. 

New trial concept proposals will be reviewed by the TrialNet SDC for scientific merit, priority, and consistency with TrialNet Strategic Plan, and by the CLC for clinical feasibility.  Studies approved by these two bodies will move forward for protocol development.  Fully developed new trials will be approved by the NIDDK, based on funding considerations, after approval by the Steering Committee. The CLC will also recommend or provide input on any TrialNet clinical operational changes.   

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.

Application Types Allowed

New
Renewal

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

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $6.5M (total cost) for up to 20 awards in Fiscal Year 2014. Future year amounts will depend on annual appropriations.

Award Budget

Application budgets are expected to average, but are not limited to, $200,000 in direct costs per year, depending on the actual needs of clinical center.

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 in response to this FOA.

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Only Non-domestic (non-U.S.) Entities (Foreign Institutions) located in North America are eligible to apply.

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

Only foreign components, as defined in the NIH Grants Policy Statement, that are located in North America 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.

Program Directors/Principal Investigators (PDs/PIs)

All PDs/PIs must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

Only PDs/PIs at institutions located in North America are eligible.

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

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:

Section IV. Application and Submission Information


1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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

Letter of Intent

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

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

The Letter of Intent, preferably electronically, 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: fc15y@nih.gov

Page Limitations

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

Required and Optional Components

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

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 with the following additions. 

Facilities and Other Resources:  Applicants should discuss their capability to participate in a distributed data entry system, since Clinical Centers should be able to interact with the TNCC to transmit and edit data.  Clinical Centers and their institutions should indicate their willingness to participate in clinical site monitoring by the TrialNet TNCC as well as other trial partners (ITN and industry).

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Applicants for TrialNet Clinical Center grants will submit budgets based on current and/or planned subject recruitment and follow-up in Pathway to Prevention and other trials. At least one Coordinator must have no less than 12 person-months effort devoted exclusively to TrialNet.  Total PD/PI effort must not exceed 3.6 person months. All PD/PI and coordinator effort should be well-justified based on current and projected clinical activity.   For renewal applications, applicants should note that co-investigators with immunology expertise are no longer specifically required.  TrialNet will be establishing a Biomarkers & Mechanisms Panel which will include consultants paid through the TNCC to provide immunologic expertise. Travel for the PD(s)/PI(s) and one coordinator should be requested for one in-person TrialNet meeting per year (in the Washington D.C. Area), plus one other scientific meeting each year to present results, engage with the research community, and exchange ideas.

Clinical Center budgets should list subject travel requests separately from all other costs.  In the Budget Justification section, applicants will describe their needs for subject travel based on prior experience and/or knowledge of the subject population likely to be enrolled and seen at their Clinical Canter or at their supported Affiliate Site(s). 

Budget Justification: Applicants should justify any resources allocated to the support of Affiliate Sites.  Budget allocations should not be solely justified based on the number of screenings accomplished by currently active Affiliate Sites since Affiliate Sites are reimbursed for screenings through the capitated payment system.  Rather, budgets should be justified based on specific activities at the Clinical Center in support of continued and enhanced Affiliate Site productivity.   For example, Clinical Center staff time traveling to Affiliate Sites to assist with screening events.

PHS 398 Cover Letter

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: Applicants should include the following information in the indicated subsections.        

Background:  Applicants should demonstrate (with reference to specific, objective sources of data on the size of the available population) access to a sufficient number of potential trial subjects with T1D or T1D risk.  For current TrialNet Clinical Centers and Affiliate Sites, a standardized recruitment report will be provided by the TNCC.  This report should not be altered and should be included as part of the Preliminary Data section.  For applicants new to TrialNet, productivity is best demonstrated by inclusion of a table describing sources and numbers of potential subjects, e.g., number of T1D patients seen annually, number of subjects currently participating in trials, the number of new T1D patients seen over the last full calendar year, and previous participation in T1D trials. A table listing the current and five most recent multi-center T1D trials that the site has participated in should be included, consisting of the following:

Complete name of the trial;

Funding source;

Name of the site PD/PI;

Time to from IRB submission to IRB approval;

Time from initiation of any contract negotiation to contract execution;

Time from IRB approval to first subject screened;

Time from IRB approval to first subject enrolled;

Enrollment rate;

Total number of subjects enrolled at the site;

Proportion of subjects lost to follow-up;

Number of protocol violations, or any other issues identified by trial monitors at the site.

Approach: The following should be included under Approach in the Research Strategy Section.  Any innovations should be identified.   

1). Leadership Statement:  Applicants should describe their leadership approach for screening, recruitment, treatment and subject follow-up in TrialNet trials and studies.  In addition, applicants should describe their vision of the challenges and opportunities in T1D prevention research currently and during the next five years. This statement will be evaluated by reviewers for leadership potential and may impact the grant score and will also be used by NIDDK to select the initial membership of the CLC

2). Collaboration Plan: Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with other Clinical Centers, the TNCC, the CNH, and the NIDDK and its partners in all aspects of TrialNet.  Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., team leadership and training, protocol adherence strategies, dissemination activities, recruitment strategies).  Applicants should describe the potential pool of co-investigators at their site as well as any Affiliate Sites they will continue to support, and the area of expertise of the co-investigators and affiliates.  There is no longer a specific requirement for immunological expertise among co-investigators at TrialNet centers, but co-investigators can be listed if they are well-justified.  Applicants should state their own willingness, as well as their team's willingness, to participate in collaborative TrialNet activities such as committees, conference calls, writing groups, meetings, etc.

3). Affiliate Site Support (optional):  If the Applicant plans to continue or to begin supporting Affiliate Sites, the applicant should indicate how co-investigators and Affiliate Sites will be identified.  Applicants should propose definite strategies for identifying those affiliates most likely to be productive, as well as plans for assessing the specific needs of Affiliate Sites and devising efficient approaches for supporting achievement of their potential.  Innovative plans for reaching out to underserved areas to find and recruit a new pool of potential subjects should be described.  

4). Recruitment and Outreach Plan:  Applicants should indicate how they will reach out to the community, referring physicians and patients. Specifically, applicants should detail actions and materials that will be used to support recruitment of subjects and should describe how subjects will be included in the conception, planning and implementation of trials so that a strong partnership between investigators and subjects can serve as a foundation for successful trial recruitment and retention.

Subject access may be accomplished by establishing links with other groups (e.g., other health care providers in the community, such as endocrinology practices, primary care practitioners, pediatricians, local hospitals, patient support groups, and health maintenance organizations) in addition to the applicant’s institution.  If links with other groups are anticipated, the application should include a plan in the Approach section of the Research Strategy with appropriate letters of support (appended in the Letters of Support section of the application) describing: (1) how the applicant Clinical Center will link to and operate with the other groups, and (2) how the Clinical Center will monitor the quality of the other group’s performance (screening, and, if applicable, subject recruitment and data collection).

The application should include a brief description of anticipated problems with recruitment and plans for addressing these problems.  Novel approaches for meeting challenges and taking advantage of opportunities to enhance screening and trial recruitment are strongly encouraged for this section of the Research Strategy.

5). Plans for Increasing Cost Efficiency:  Applicants should describe plans for maximizing operational cost efficiency on a per-subject basis.  Applicants should evaluate their per-subject cost efficiency for screening, recruitment, follow-up and retention. In addition, they should identify opportunities for improvements, as well as challenges.  For example, plans for supporting Affiliate Sites for trial follow-up could realize travel cost savings while also decreasing subject burden and increasing recruitment. 

6). Plan for Use of a Central or Federated IRB:  For new trials, and new Affiliate Sites, plans to reduce start up time by increasing the efficiency of contracting and IRB review through use of federated IRB models should be described. Applicants and their institutions should indicate their willingness to participate in a federated IRB model with the option to designate one central IRB as IRB of record as an efficient alternative to the currently prevalent local review of the initial protocol and progress reports and adverse events. The concurrently competed CNH will be funded to coordinate a central IRB of record and manage all required IRB communication and documentation including, but not limited to, tracking approval, maintaining regulatory documents, communications with local IRBs, and handling adverse event reporting and notifications.  Applicants should indicate their willingness to work with the CNH on IRB submissions.

7). Performance Monitoring and Potential Interventions Plan:  The application should include a plan for how the PD(s)/PI(s) will monitor performance, recruitment and retention (in collaboration with the TNCC) for new and ongoing TrialNet trials at the Clinical Center and Affiliate Site network (when applicable).

8). Plan For Development Of New T1D Clinical Researchers:  The TrialNet network provides a rich environment for early stage or new investigators to develop research skills and to assist them in progressing to more senior status.  Applicants should describe plans to reach out to early stage or new investigators.

Letters of Support: Letters of support from potential co-investigators at the applicant's site and at current or proposed affiliates, affirming an interest in collaborating with the potential PD(s)/PI(s) and with the network as such, describing their expertise, track record, interest, and access to patient populations, should be included in the separate Letters of Support section of the application.

An institutional letter of support from the applicant's departmental and/or institutional leadership should be included in the Letters of Support section of the application.

Letters of Support from the TrialNet Coordinating Center are not required, even for new Clinical Centers.  TrialNet is a collaborative project and collaborative agreements, as needed, will be developed after applications are reviewed and prior to award.

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 modifications:

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 Institutions

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

3. Submission Dates and Times

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

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

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

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

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

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

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

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIDDK, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed. 

In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at fcy15@mail.nih.gov  when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post-Submission Materials

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

Section V. Application Review Information


1. Criteria

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

For this particular announcement, note the following additional criteria.

Review criteria for Clinical Center U01 awards will include, in part, past productivity in TrialNet for competing continuation applications, or other type 1 diabetes trials for new applications, as well as plans for future productivity in T1D screening and prevention trial conduct (especially novel approaches to increase trial recruitment). In addition, reviewers should evaluate the merit of the "Leadership Statement” describing the PD/PI vision for the future of T1D prevention research.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Investigator(s)    

Are the PDs/PIs, 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? 

Is innovation demonstrated in approaches for maximizing screening and trial recruitment and retention? 

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?

Does the application provide assurance that the institution will attempt to utilize a central IRB of record?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the 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

Not Applicable

Renewals

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

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

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

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:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

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

Section VI. Award Administration Information


1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

The PD/PIs or their representatives from funded components of TrialNet, e.g., TrialNet Data Coordinating Center, the Screening Clinical Network Hub, and the TrialNet Clinical Centers, will jointly have the primary responsibility for:

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

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

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

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

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

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

7. Establishing procedures, where applicable, for all participating institutions in coordinated awards to comply with FDA regulations for studies involving investigational agents or devices and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects, and the NIH policy requirements for the inclusion of women, minorities and children.

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

9. Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIDDK support; or special access to study results, primary data/summary information, or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party is permitted only after concurrence by NIDDK.

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

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

12. The NIDDK has established Central Biosample, Genetic, and Data Repositories for the

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

13.  The Food and Drug Administration Amendments Act of 2007 (FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law requires mandatory registration and results reporting for certain clinical trials of drugs, biologics, and devices. If trials conducted under this grant are applicable clinical trials subject to FDAAA, the sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors (http://www.icmje.org/publishing_10register.html).

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

An NIDDK Project Scientist with substantial involvement will:  

1. Serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist or Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Have substantial involvement assisting in the design and coordination of research activities for awardees as elaborated below:

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

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

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

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

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

Interact with the principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, data safety and monitoring board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.

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.

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.

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.

Appoint a Data and Safety Monitoring Board (DSMB) as appropriate; the NIDDK Program Official or their designee will serve as the Executive Secretary and/or NIDDK program representative on the DSMB.

Joint Responsibilities

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

1. Steering Committee.

A Steering Committee organized by the study investigator(s) will be the main governing body of the study.

The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, questionnaires and other data recording forms, establish and maintain quality control among awardees, review progress, monitor patient accrual, coordinate and standardize data management, and cooperate on the publication of  results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official, and will provide periodic supplementary reports upon request.

The Steering Committee will be composed of all PD/PIs, (including those of data coordinating /statistical centers, if any) and co-investigators as deemed necessary, and the NIDDK Project Scientist. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee.

A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings, representing the study group to the External Oversight Committee established by the NIDDK (see item D2 below) and by interacting closely with the awardees during protocol development and implementation.

2. External Study Oversight.

An independent Data and Safety Monitoring Board will be established by the NIDDK for Phase III clinical trials or other high risk studies as appropriate. An Observational Study Monitoring Board (OSMB) will be established for observational/epidemiologic studies. These Boards will review study progress, safety data and interim results, as appropriate, and provide guidance to the NIDDK.

Dispute Resolution

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

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Scientific/Research Contact(s)

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

Peer Review Contact(s)

Francisco Calvo, Ph.D.
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8897
Email: fc15y@nih.gov

Financial/Grants Management Contact(s)

Diana O'Donovan
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8868
Email: odonovand@extra.niddk.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


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