Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

The Type 1 Diabetes TrialNet Coordinating Center (TNCC) is responsible for supporting the development and implementation of observational studies, clinical trials, and associated mechanistic studies conducted by the TrialNet network of Clinical Centers and associated clinical sites (Affiliates Sites), for direction of communication and coordination among the Clinical Centers and Affiliate Sites, and for management of the collection and analysis of genetic, immunologic, pathogenic, clinical and biological samples and data from the clinical sites. The TNCC is also responsible for: 1) support of study protocols and Manuals of Operation for each TrialNet study; 2) maintaining the TrialNet internal and public websites; and 3) organizing TrialNet Steering Committee meetings, Data Safety Monitoring Board (DSMB) meetings, External Evaluation Committee (EEC) meetings, and other meetings and workshops as necessary. In addition, the TNCC is responsible for transferring all data and biosamples that are the property of NIDDK to the appropriate NIDDK repositories.

The TNCC is responsible for:

• oversight and coordination of Clinical Center activities, including supporting development of the Clinical Centers and implementing observational studies, clinical trials, and associated mechanistic studies conducted by the network of Clinical Centers and associated Affiliates Sites;
• oversight of implementation of and adherence to study protocols;
• coordination of communication among and with the Clinical Centers and Affiliate Sites;
• management of the collection and analysis of genetic, immunologic, pathogenic, clinical and biological samples and data from the clinical sites;
• training and certification of study staff, and maintenance and updates of the Manuals of Operations for each TrialNet trial
• maintaining the TrialNet internal and public websites;
• organizing and preparing reports for TrialNet Steering Committee meetings, Data Safety Monitoring Board (DSMB) meetings, External Evaluation Committee (EEC) meetings, and other meetings and workshops as necessary;
• collection and management of all clinical and laboratory data, and for ensuring subject confidentiality, safety and quality control;
• ensuring that the design of the study, including the primary outcome, is scientifically sound and is supported by appropriate power calculations;
• providing biostatistical and analytic expertise, and conducting data analysis and interpretation (in conjunction with the TrialNet Clinical Center investigators) of the laboratory and clinical data generated by TrialNet studies;
• guiding development of the statistical analysis plan for each TrialNet study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes;
• overseeing and facilitating communication between the Drug Distribution Center and the Clinical Centers (and Affiliate Sites) to ensure the timely supply of medications according to the protocols;
• transferring all data and biosamples generated from TrialNet studies to the NIDDK Central Repository per NIH and NIDDK Resource Sharing policies;
• engaging a broader set of investigators external to the immediate study group to provide opportunities to analyze the data and participate in the parent study by means of ancillary studies;
• developing opportunities for local analysis of data by study investigators and other qualified researchers at their institutions, and investigators outside the study group ("disseminated data analysis"); and
• agree to abide by the Network Duality of Interests Policy and Procedures and may be asked to develop procedures to require study investigators and others associated with the study to identify financial and other conflicts of interest on a routine basis, at least annually, and share this information with the NIDDK Program staff.

The TNCC will select Clinical Centers to screen the necessary number of relatives of individuals with T1D and to enroll those eligible and interested into TrialNet prevention and new-onset studies.

• It is expected that approximately 10 to 15 Clinical Centers will be selected, and that the total funds to be allotted for support of the Clinical Centers will be approximately $6,500,000 annually (total cost; $4,200,000 direct cost). This amount may vary over the duration of the grant and is dependent on the availability of funds and the number of ongoing trials.
• It is anticipated that this competition will accommodate Clinical Centers across a wide range of funding levels.
• Some, but not all, Clinical Centers will oversee Affiliate Sites. Clinical Center/Affiliate Site distribution will be organized to optimize coverage of North America.
• Successful Clinical Center applicants will demonstrate the ability to efficiently screen, recruit, treat and follow subjects in T1D prevention trials. They should incorporate active and innovative approaches to improving screening and enhancing trial participation.
• Clinical Center Program Directors/Principal Investigators (PDs/PIs) are 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 must have expertise in T1D etiology and pathogenesis as well as the willingness to engage in potentially challenging but scientifically strong interventions and studies that advance the field toward its goal of T1D prevention.
• Clinical Centers will be chosen based on their ability to screen and recruit trial participants and implement study protocols.
• Only applications from Institutions willing to utilize TrialNet's central IRB (OneIRB) should be considered (this applies to U.S. sites only). Only PDs/PIs located at North American institutions will be eligible to apply in response to the RFP issued by the TNCC.
• Clinical Centers must propose at least one Coordinator at no less than 6 person-months devoted exclusively to TrialNet. Total PD/PI effort must not exceed 3.6 person-months.
• Funding levels for Clinical Centers selected will be re-evaluated yearly based on individual site productivity and available opportunities.
• Funded Clinical Centers must demonstrate an intention to actively participate in all TrialNet studies and trials and to participate, when possible, in Living Biobank studies, ancillary studies and partnered new onset trials
• Geographic distribution of network centers should be considered in the choice of Clinical Centers to ease subject burden and reduce network costs related to travel.

This Funding Opportunity Announcement (FOA) will support the existing TNCC to continue oversight of TrialNet's ongoing screening efforts, prevention studies and new-onset studies, and to manage the development and implementation of new TrialNet prevention and new-onset studies. The TNCC will issue one or more RFPs to select (via open competition) and fund (via subcontracts) approximately 10-15 North American TrialNet Clinical Centers (previously funded by individual cooperative agreements) to support subject recruitment into trials and studies, trial conduct, subject retention and follow-up. Funds will be provided to Clinical Centers for staff time, personnel travel to TrialNet meetings, patient travel to TrialNet sites for study participation, and activities in support of Affiliate Sites. Clinical Centers and Affiliate Sites will also be supported for screening and patient care costs through per-patient per-visit capitated payments from the TNCC. In addition, the TNCC will fund (via subcontract) the TrialNet Chair Office and TrialNet central laboratories and support units .

Background

Type 1 diabetes (T1D) is a serious and burdensome chronic disease that usually has onset in childhood or early adulthood. Rates of T1D are rising worldwide. TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of T1D. TrialNet researchers are striving to prevent T1D through better characterization of the natural history of the disease, identification of persons at early, non-symptomatic stages of disease, and clinical evaluation of exciting new therapies that balance potential risks and benefits. 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 interventions aimed at interdicting the T1D disease process prior to clinical diagnosis (in new-onset disease).

TrialNet tests interventions aimed at decreasing -cell destruction and/or enhancing -cell survival. To identify individuals for prevention trials, TrialNet must screen about 15,000 new relatives of individuals with T1D each year.

TrialNet, a large, complex, highly collaborative clinical trials network, currently consists of 17 North American Clinical Centers (funded by NIDDK cooperative agreements), six international Clinical Centers (infrastructure funded by Juvenile Diabetes Research Foundation [JDRF]), a 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, following award of this cooperative agreement, the TNCC will issue RFP (s) to select the North American TrialNet Clinical Centers, which will be funded via TNCC subcontracts. The TrialNet Chair's 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. They receive only capitated per-subject per-visit payments from the TNCC. 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 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 -cell production.

In addition to the TrialNet Pathway to Prevention Study, which screens relatives and monitors those found to be at risk, TrialNet has multiple prevention and new-onset trials which are ongoing or under development, some of which are expected to commence prior to the new award. 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, which enables intervention earlier in the disease process as well as decreasing trial duration and sample size.

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

*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)

Research Objectives

During this 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 subjects not currently eligible for ongoing trials. TrialNet also plans to 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.

The TrialNet Steering Committee, consisting of investigators from the TrialNet Clinical Centers, the TNCC, the NIDDK Project Scientist and representatives from the TrialNet Collaborative Mechanistic Studies Panel (CMSP), collaboratively selects, develops and implements TrialNet clinical trials. The TrialNet Study Group jointly analyzes data from studies and disseminates findings through presentations at scientific meetings and through manuscripts published in scholarly, peer-reviewed journals. The Study Group has developed a variety of mechanisms through which investigators outside of the study group may collaborate with the TrialNet Study Group to test novel hypotheses using the TrialNet cohort or TrialNet samples and/or data.

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

Limited recompetition of the TNCC is being conducted concurrently with an open recompetition for the HUB through a separate FOA (RFA-DK-18-008). Following this award, the TNCC will conduct an open competition to select and fund (via subcontracts) the North American TrialNet Clinical Centers. Applicants to the HUB and TNCC opportunities are strongly encouraged to contact the NIH Program Official listed below before preparing an application. In addition, NIH staff will lead webinars, as needed, to describe and answer questions about this opportunity and TrialNet.

1. TrialNet Clinical Centers

The TrialNet Clinical Centers are responsible for screening relatives of individuals with T1D, enrolling individuals into the Pathway to Prevention monitoring study, and recruiting eligible, interested subjects into TrialNet prevention and new-onset studies. TrialNet Clinical Centers enroll, treat and retain TrialNet prevention and new-onset study participants. Some TrialNet Clinical Centers support TrialNet Affiliate Centers. Clinical Centers regularly interact with the TNCC, the HUB, the NIDDK and its partners.

Clinical Centers are responsible for implementing all TrialNet protocols. The Clinical Centers are expected to collect data in accordance with established study procedures and submit all samples and data to the TNCC and central laboratories as appropriate and required by the protocols.

Investigators at the Clinical Centers conduct analyses in conjunction with the TNCC. The TrialNet Study Group has exclusive access to data from TrialNet studies for a defined period, according to NIDDK data sharing policies. All study data analyzed for publication of the primary study outcome(s) are expected to be provided to the NIDDK Repository so that it can be shared within six months of the publication date for the primary outcome manuscript or within two years of the date that the database is locked for analysis, whichever occurs first. All data analyzed for publication of secondary outcomes are expected to be provided to the Repository so that it can be shared within two years of the date that the database for these outcomes is locked for analysis. All study data must be provided to the NIDDK Repository at the end (or prior to the end) of each grant cycle. Data will not be released until proprietary periods have passed. The TrialNet Study Group has established policies under which ancillary and living biobank studies may be conducted while the study is ongoing.

2. TrialNet Coordinating Center (TNCC) (see description above)

3. TrialNet Steering Committee

The primary governing body of the TrialNet network continues to be the Steering Committee, comprised of the Clinical Center PDs/PIs, the TNCC PD/PI, the TrialNet Chair, the HUB PD/PI, and the NIDDK Project Scientist. In addition, 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. CMSP membership will be determined by the TrialNet Executive Committee, consisting of the TNCC PD/PI, the TrialNet Chair, the TrialNet HUB PD/PI and the NIDDK Project Scientist.

The TrialNet Steering Committee is responsible for designing network research activities, establishing priorities, developing common protocols and manuals, questionnaires and other data recording forms, establishing and maintaining quality control among awardees, reviewing progress, monitoring patient accrual, coordinating and standardizing data management, and cooperating 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 Director, and will provide periodic supplementary reports upon request.

4. TrialNet Chairperson

A Chairperson of the Steering Committee, other than the NIDDK Project Scientist, will be selected by NIDDK. The Chairperson functions as the scientific coordinator for network trials and provides leadership to the Steering Committee by conducting Steering Committee meetings, representing the study group to the External Evaluation Committee (EEC) established by the NIDDK, and by interacting closely with members of the Steering Committee during protocol development and implementation. The TrialNet Chairperson serves for a term of five years. NIDDK may opt to select the same Chairperson for more than one five-year term.

5. TrialNet Clinical Network Hub (HUB)

Open recompetition of the TrialNet HUB is being conducted concurrently with the TNCC limited competition. The HUB is responsible for developing and leading a coordinated program to enhance risk screening, recruitment, conduct and retention for TrialNet’s prevention and new-onset trials.

During the analysis and publication phase of TrialNet studies, the HUB is responsible for working with the TNCC and network investigators in the publication of manuscripts.

The HUB coordinates and manages TrialNet central IRB communication and documentation, and is responsible for overseeing all network communication and coordination.

The HUB PD/PI participates on the TrialNet Executive Committee and is a member of other network working groups. The HUB works closely with the TNCC, Clinical Centers and Chairperson’s Office in a collaborative and interactive manner.

6. NIDDK Project Scientist

The NIDDK Project Scientist assists the Steering Committee in carrying out all TrialNet studies. The Project Scientist provides scientific support to awardee activities, including protocol development, quality control, interim data monitoring, final data analysis, preparation of publications, and overall performance monitoring.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

This FOA is limited to the current T1D TrialNet Coordinating Center awardee supported under RFA-DK-17-507.

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.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 the PD/PI of the current Coordinating Center for TrialNet, RFA-DK-17-507, is eligible to apply to this FOA.

2. Cost Sharing

3. Additional Information on Eligibility

Number of Applications

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

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: [email protected]

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

Research Strategy:

Significance: Type 1 Diabetes TrialNet is an ongoing network, and its studies and progress are reviewed annually by an External Evaluation Committee. The applicant should briefly explain the network's continued importance, critical need, scientific premise and impact.

Innovation: Plans for continued innovation with respect to type 1 diabetes clinical trials and network operations should be provided.

Approach: The applicant should describe plans to support the research being performed by the Type 1 Diabetes TrialNet network, including: (1) screening of relatives of individuals with type 1 T1D for monitoring and possible inclusion in intervention studies aimed at preservation of insulin-producing cells; (2) the design, conduct and continuation of intervention studies in individuals at risk for the development of T1D and in individuals with new-onset T1D (as selected by the TrialNet Steering Committee); (3) a wide range of research projects in varying stages of development, implementation and completion; (4) data and sample management, including standardized acquisition, quality control, dissemination, and public accessibility; and (5) management and collaborative leadership within the structure of the TrialNet network. In addition, the applicant should describe their plans for: (1) issuing one or more RFPs and subsequ ent selection of the TrialNet Clinical Centers, and (2) monitoring of and quality assurance for the performance of the Clinical Centers throughout the project period.

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)). Because current and prospective Clinical Centers will be submitting applications in response to the RFP(s), letters of support from current and prospective TrialNet Clinical Center personnel should not be provided.

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.
• The TNCC application should include an overall sharing plan for data generated during the funding of TrialNet. The plan should specifically indicate what will be shared, by what means it will be shared, and the conditions that will apply to recipients of shared data.

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.

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

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.

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.

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Significance

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 scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA: Does the PD/PI explain the network's continued importance, critical need, scientific premise and impact?

Investigator(s)

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?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA: Does the PD/PI provide consistent evidence for collaborative leadership, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA?

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?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA: Is the plan sufficient for continued innovation with respect to type 1 diabetes clinical trials and network operations?

Approach

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?

Does the PD/PI adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA:

Are the plans and strategies satisfactory for: (1) the screening of relatives of individuals with T1D for monitoring and possible inclusion in intervention studies aimed at preservation of insulin-producing cells; (2) the design, conduct and continuation of intervention studies in individuals at risk for the development of T1D and in individuals with new-onset T1D (as selected by the TrialNet Steering Committee); (3) a wide range of research projects in varying stages of development, implementation and completion; (4) data and sample management, including standardized acquisition, quality control, dissemination, and public accessibility; and (5) management and collaborative leadership within the structure of the TrialNet network?

Are the plans and strategies adequate for the issuance of one or more RFPs and subsequent selection of the TrialNet Clinical Centers and for the monitoring of and quality assurance for the performance of the Clinical Centers throughout the project period?

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?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the PD/PI adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the PD/PI adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

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

Revisions

Not Applicable

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

• Will receive a written critique.

• 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

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

Section VI. Award Administration Information

1. Award Notices

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

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.

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 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 Program Directors/Principal Investigators (for studies involving multiple protocols) shall designate 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. Implementing collection of data specified by the study protocol. For a multi-center study, each awardee/site is required to ensure that data will be submitted expeditiously to the Data Coordinating Center. Additionally, individual investigators/sites must demonstrate the ability to implement the strategy specifically designed for their individual study population.

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

6. Submitting interim progress reports, when requested 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 coordinate 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 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 sponsor or his/her designee will perform the mandatory study registration and reporting of study results to ClinicalTrials.gov. For more information about this law and requirements for sponsors and/or investigators, visit the PRS and U.S. Public Law 110-85 Information Page at http://prsinfo.clinicaltrials.gov/fdaaa.html. In addition, grantees should be aware that clinical trials not covered by FDAAA may still require registration in an approved registry in order to be published, according to the guidelines issued by the International Committee of Medical Journal Editors ( http://icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-registration.html).

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 NIDDK 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.
   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
5. 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

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

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: [email protected] (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: [email protected]

Section VIII. Other Information