Part 1. Overview Information

Key Dates

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Research progress in the treatment for diseases of the exocrine pancreas [chronic pancreatitis (CP), pancreatogenic diabetes mellitus, and pancreatic cancer] has been hampered by the disorders' heterogeneity, the limitations of previous small cross-sectional studies, the inability to safely obtain pancreatic tissue for discovery, and the lack of structured epidemiology tools, genetic testing, and biomarker development and validation. Mechanism-based research of these diseases has suffered from the lack of systematically collected clinical measures in longitudinal cohort studies linked with biospecimens. Given the increasing incidence and prevalence of CP and its association to the development of pancreatic cancer, its complications, high mortality rate, and associated health care cost, the National Institute for Diabetes and Digestive and Kidney Diseases and the National Cancer Institute established in 2015 the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) Consortium as multidisciplinary teams composed of members from the Clinical Centers and Coordination and Data Management Center to undertake a comprehensive clinical, epidemiological, and biological characterization of patients with CP (including adults and children with recurrent acute pancreatitis) to develop treatments and gain insight into the pathophysiology of CP and its sequela: chronic pain, pancreatic exocrine and endocrine insufficiency, T3cDM, and the diabetes/pancreatic cancer association. Another objective was to undertake studies on the development of pancreatic cancer in newly diagnosed diabetic patients (https://www.ncbi.nlm.nih.gov/pubmed/30325859). During the current funding, the CPDPC is conducting 3 longitudinal clinical studies:

A. Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) (https://www.ncbi.nlm.nih.gov/pubmed/30325862).

B. Pediatric Longitudinal Cohort Study of Chronic Pancreatitis [The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE 2)] (https://www.ncbi.nlm.nih.gov/pubmed/30325861).

C. A Prospective Study to Establish a New Onset Diabetes (NOD) Cohort (https://www.ncbi.nlm.nih.gov/pubmed/30325864).

Through the continuous enrollment of well-characterized patients and associated biospecimens (blood, pancreatic and duodenal juice, urine, stool and pancreatic tissue) the CPDPC research will provide the resources and collaborative opportunities necessary for development of more effective treatments, discovery of drugs, biomarkers, and achieving many of the research objectives identified in the strategic plans of the participating NIH institutes.

In addition to above clinical longitudinal studies, i.e., PROCEED, INSPPIRE 2, NOD, the consortium developed two additional studies to better define and characterize pancreatogenic diabetes (T3cDM);

1. Evaluation of a mixed meal test for Diagnosis and characterization of Pancreatogenic Diabetes secondary to pancreatic cancer and chronic pancreatitis (DETECT) (https://www.ncbi.nlm.nih.gov/pubmed/30325863).

2. Detailed Physiologic Characterization of the Insulin Axis in Type 3c Diabetes versus Type 2 Diabetes (DEPICT 3v2).

Research Objectives

Through completion of the clinical studies initiated since the establishment of the CPDPC, the overriding two objectives of this consortium continue to be the pursuit of clinical research (1) on Chronic Pancreatitis (including those with Acute Recurrent pancreatitis, ARP), by identifying and characterizing a large cohort of pediatric and adult patients with CP and ARP to encourage translational research that will provide the basis for understanding the natural history and developing means of diagnosis, treatment and clinical management of Chronic Pancreatitis and its sequela: chronic pain, pancreatic insufficiency and (2) on pancreatic cancer and pancreatogenic Diabetes Mellitus (T3cDM) and their pathogenic interrelationships, by identifying and following a cohort of newly diagnosed diabetic patients. In addition, the pathogenic interrelationships of pancreatogenic Diabetes Mellitus (T3cDM) in the setting of CP.

Applicants for a Clinical Center will provide information regarding their potential contributions to one or several of the longitudinal studies ongoing in the CPDPC (listed above) and can propose ancillary studies in their individual applications, for post-award consideration by the Consortium Steering Committee. Examples of objectives that are appropriate include, but are not limited to:

• Genome-wide studies to identify markers for treatment response and development of fibrosis in patients with acute or acute recurrent pancreatitis who progress to CP.
• Evaluation of non-invasive methods to detect, quantify, and measure treatment response in pancreatic fibrosis.
• Defining profiles of disease progression in Chronic Pancreatitis and its implication for treatment response
• Role of genetic risk factors in early onset CP, and its implication for prognosis, and treatment response
• Altered Microbiome and Genome in Pancreatitis, Diabetes, and Pancreatic Cancer
• Propose clinical trials specific to disease subtypes to determine efficacy of treatment strategies to improve patient reported symptoms and patient centered outcomes: anti-fibrosis in patients with suspected (early) CP; pharmacological interventions for the prevention of diabetes and pancreatic cancer in patients with CP and for the treatment of T3cDM. .
• Clinical trials for treatment of pain, depression, improved quality of life in the pediatric and adult CP populations
• A randomized controlled trial of internet-based pain self-management for persons with acute recurrent and chronic pancreatitis pain
• Precision medicine approaches for better diagnostic, prognostic, and treatment choices for affected populations
• Studies to establish the incidence, prevalence, and methods for diagnosis, prognosis, treatment of pancreatogenic (type 3c) diabetes (T3cDM), and to evaluate T3cDM as a possible harbinger, or biomarker, of pancreatic cancer.
• Studies to establish the risks of acute/chronic pancreatitis and pancreatic cancer in patients with Type 2 (T2DM) and Type 3 (T3cDM) diabetes and those treated with incretin-based therapy.
• Studies to establish the incidence and prevalence of pancreatogenic (type 3c) diabetes (T3cDM).
• Evaluate T3cDM as a biomarker for the early detection/diagnosis of pancreatic cancer and the development of biofluid-based tests for pancreatic cancer.
• Studies to establish the incidence, prevalence, and methods for diagnosis of pancreatic cancer in New-onset diabetes and to evaluate diabetes as a possible harbinger, or biomarker, of pancreatic cancer.
• Studies addressing the mechanisms by which PDAC causes pancreatogenic (type 3c) diabetes (T3cDM)
• Studies proposing identification of patients at "higher risk" for the development of pancreatic cancer within the NOD subjects, through development of biomarkers, algorithms etc.

Organization of the Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) Consortium

The CPDPC Consortium will consist of the following entities: the NIH, all Clinical Centers (CCs), a Coordination and Data Management Center (CDMC), an Executive Committee, a Steering Committee and its subcommittees, a Data and Safety Monitoring Board (DSMB), and other committees as needed. The responsibilities of each entity of the Consortium are described in the Terms and Conditions of Award.

The NIDDK, in consultation with the NCI, is responsible for organizing and providing support for the CPDPC and is involved substantially with the awardees as a "partner," consistent with the Cooperative Agreement mechanism. A designated NIDDK and NCI Project Scientist will provide programmatic oversight, monitor subject recruitment and study progress, ensure disclosure of conflicts of interest and adherence to applicable NIH, NIDDK and NCI policies. The NIDDK, in consultation with the NCI, appoints the Chairperson(s) of the Steering Committee and all members of the DSMB. An additional NIDDK Program Official will be responsible for the programmatic stewardship of the award and will be named in the award notice.

Through subawards and/or involvement of appropriate clinical departments within an applicant institution, Clinical Center applicants are encouraged to involve investigators interested in both Adult and Pediatric pancreatology to contribute to any consortium-wide approved study and particularly to the completion of one or several of the clinical studies currently ongoing in the CPDPC:

PROCEED (https://www.ncbi.nlm.nih.gov/pubmed/30325862),

INSPPIRE 2 (https://www.ncbi.nlm.nih.gov/pubmed/30325861), and/or

NOD Cohort (https://www.ncbi.nlm.nih.gov/pubmed/30325864).

All CC Program Directors/Principal Investigators (PDs/PIs) are strongly encouraged to fully commit their center resources and efforts to the Consortium protocols and will disclose to the Steering Committee any institutional specific clinical studies that may overlap with the clinical activities of the CPDPC Consortium. The CCs will continue to recruit subjects into any approved consortium studies and will conduct the clinical trials and longitudinal follow-up as described in the study protocols. No deviations will be allowed. All individual CCs will be required to participate in a cooperative and interactive manner with one another, with the CDMC, and with the NIH in all aspects of the Consortium (see Terms and Conditions of Award). Only investigators who wish: to continue to carry out the protocols of the CPDPC Consortium; state their willingness to disclose other center specific clinical studies that may overlap the activities of the CPDPC Consortium; are open to the concept of a single Institutional Review Board for the overall consortium; and agree to be governed by the policies and procedures of the CPDPC and its steering committee should apply to this FOA.

Study Governance

Steering Committee. The Steering Committee is the main governing body of the CPDPC Consortium (see Terms and Conditions of Award). The Steering Committee is composed of the PDs/PIs of each CC in the Consortium, the PDs/PIs of the CDMC, the NIDDK and NCI Project Scientists and the NIDDK Program Official. The Steering Committee Co-Chairs are appointed by NIDDK, in consultation with the NCI. The Steering Committee will have primary responsibility for the general organization of the Consortium and approval of studies, publications and ancillary studies. The Steering Committee will be responsible for the conduct and monitoring of studies and reporting study results. Topics for investigational and treatment protocols will be proposed and prioritized by the Steering Committee. Other subcommittees of the Steering Committee will be established and will operate as necessary, such as publications, ancillary, protocol, pathology and radiology. All face to face Steering Committee, DSMB, and other necessary face to face meetings requiring the presence of NIDDK and NCI personnel will be held in the Washington, DC/Baltimore metropolitan area or other suitable venue.

Executive Committee. An Executive Committee will be comprised of Steering Committee Co-Chairs (appointed by NIDDK, in consultation with the NCI), the PD/PI of the CDMC, the NIDDK and NCI Project Scientists, and NIDDK Program Official. The Chair of the Executive Committee will be appointed by the NIDDK, in consultation with the NCI. The Executive Committee will be convened to effect management decisions required between Steering Committee meetings, as required for the function of the Consortium. Other NIDDK, NCI, and CDMC personnel, as deemed necessary by the Project Scientists and Program Official, may also be included.

Data and Safety Monitoring Board. An independent Data and Safety Monitoring Board (DSMB) will be established by the NIDDK, in consultation with NCI to review protocols and monitor patient safety and performance of each study. As a part of its responsibilities, the DSMB will submit recommendations to the NIDDK regarding the feasibility and continuation of each study. The DSMB will be responsible for final approval of the Data and Safety Monitoring Plan developed by the CDMC. All protocols or changes to protocols will be approved by single Institutional Review Board (sIRB) through reliance agreements at all participating centers and satellite sites, the Steering Committee, the CPDPC Data and Safety Monitoring Board, and the NIDDK and NCI before initiation.

Other Special Performance Requirements

The CPDPC Consortium will continue to be a collaborative effort that requires frequent interactions of awardees among themselves and with the NIDDK/NCI Program Directors. Applicants are expected to:

• Participate in Steering Committee meetings (expected to occur in person two times a year in the Washington DC/Baltimore metropolitan area or other suitable venue, and as monthly (or as needed) teleconferences, site visits as required by the NIDDK/NCI and regular subcommittee telephone conference calls);
• Cooperate with other awardees in the development and design or modification of research protocols, and cooperate with other awardees in carrying out approved research protocols and disclose to the Steering Committee any applicant institutional specific clinical studies that may overlap with the clinical activities of the CPDPC consortium
• Abide by common definitions; common methods for patient selection and enrollment; and common protocols, procedures, tests, and reporting forms as chosen by majority vote of the Steering Committee;
• Actively seek to implement each consortium-wide protocol approved by the DSMB and the NIDDK and NCI that the site is selected for participation;
• Comply with all study policies and quality assurance measures approved by the Steering Committee;
• Agree to cede / rely on a single Institutional Review Board for the overall consortium;
• Agree to oversight of the study by a Data and Safety Monitoring Board (DSMB);
• Transmit study data to the Coordinating and Data Management Center in a timely and accurate manner;
• Transmit biospecimens to the CPDPC biobank, as well as to the NIDDK and NCI central repositories
• Report all adverse events in accordance with procedures established by the Steering Committee, and NIDDK and FDA policies;
• Cooperate with other awardees in the publication of study results and the eventual release to the scientific community of study procedures and other resources;
• Serve on and chair subcommittees and protocol committees as assigned by the Steering Committee or the NIDDK or the NCI; and
• Accept the Cooperative Agreement Terms and Conditions of Award in Section VI.2.A Award Administration Information .

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations

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 to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration , but all registrations must be in place by time of submission. 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

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

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

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, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: [email protected]

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

with the following exceptions or additional requirements:

For this specific FOA, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: There should be evidence of strong institutional support for the CC, including adequate space in which to conduct clinical and research activities and office space for staff. Institutional resources for patient care and follow-up including personnel, space, and special laboratory facilities should be described in the CC application.

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

An organizational structure for the CC should be set forth in the application, delineating specific personnel (e.g., pathologists, radiologists, etc.) available to carry out the longitudinal studies currently approved by the CPDPC (see background section above and https://cpdpc.mdanderson.org/clinicalstudies.html) and any ancillary study proposed.

All proposed key personnel must demonstrate the capability to provide substantial scientific expertise that is consistent with and aligns with the objectives of the Consortium. The final decision on the acceptance of the additional scientific personnel will be at the discretion of the NIDDK/NCI based upon consortium objectives and the availability of support. The PD/PI should state his/her general support of collaborative research and interaction with the NIDDK/NCI, the other CCs, and the CDMC as described in the collaborative agreement

R&R or Modular Budget

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

Investigators must submit a complete, justified, individual budget for each year of support requested. All costs requested and all changes in budgets after the first year should be clearly identified and justified. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating site, if multiple sites or cores are proposed. (see Letters of Support in the PHS 398 Research Plan below).

Funds to support patient enrollment cost for the different studies the applicants will contribute, is not to be included in the $300,000 direct cost limit, as it will be provided via the CDMC based on negotiated study-specific statements of works and the availability of funds.

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

Research Strategy: The Clinical Center (CC) PD/PI should describe their willingness to collaborate with other members of the Consortium, the Coordination and Data Management Center (CDMC), the CPDPC Biobank, the Data and Safety Monitoring Board and the NIDDK Central repository. CC applicants (including sub awardee sites) should describe how they will be able to submit data to the Coordinating and Data Management Center and biospecimens to the NIDDK Repositories (supported by an independent contract from NIDDK) and to central laboratories and biological cores as approved by the Steering Committee. CCs should show how they will work in collaboration with the CDMC to implement procedures for uniform data collection, handling and transmittal of data, as well as data audits and other data quality control procedures, as established by the study protocol.

CCs should also provide information regarding future plans for involvement with operational committees of the Consortium (e.g. Recruitment, Publications, etc.) and the establishment of uniform procedures and policies.

Applicants should document their ability to recruit patients, procure specimens prospectively, collect epidemiological and clinical data using previously developed Common Data Elements to contribute to the completion of one or several of the longitudinal clinical studies currently undergoing in the CPDPC: PROCEED (https://www.ncbi.nlm.nih.gov/pubmed/30325862), INSPPIRE 2 (https://www.ncbi.nlm.nih.gov/pubmed/30325861), and/or NOD Cohort (https://www.ncbi.nlm.nih.gov/pubmed/30325864). For the NOD study, a multidisciplinary team with expertise in pancreatic cancer, diabetes, clinical research, early detection, and/or screening/surveillance is required. The application should include a dedicated PI/clinician and dedicated research coordinator, demonstrate the ability to recruit patients into the NOD study, provide an estimate of number of patients with NOD in their catchment area, demonstrated interaction with Primary Care Physician’s in their healthcare system and IT support for application of a generic algorithm for identification of NOD patients using the EMR (Electronic Medical Records) of the associated healthcare system (algorithm to be provided).

In addition to the standard background, significance, innovation, and approach that must be discussed in the Research Strategy, the applicants should describe in detail the number of potential patients eligible for any of the studies cited above, the CC is interested to participate in, as well as a description of barriers and proposed solutions to fulfil the recruitment targets for each study.

Letters of Support: If parts of the costs of the application are to be borne by sources other than NIH, these contributions must be presented in detail along with supporting letters signed by individuals who have the authority to make fiduciary commitments on behalf of the institution. These outsource costs do not constitute cost sharing as defined in the current NIH Grants Policy Statement and should not be presented either as part of the requested budget or as Estimated Project Funding.

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research

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

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

To be considered highly meritorious, an application does not have to contribute to all the ongoing studies CPDPC studies (PROCEED, INSPPIRE 2, NOD, DETECT, and DEPICT 3v2.

For this particular announcement, note the following:

In addition, for applications involving clinical trials

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed). Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, for applications involving clinical trials

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:

Although Ancillary Study (AS) proposed may be considered preliminary until accepted by the consortium, does the AS proposed in the application (whether clinical trials or not) address an important problem in the field?

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?

In addition, for applications involving clinical trials

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:

Are the Program Directors/Principal Investigators (PDs/PIs) and their institutions clearly committed to provide their center resources and efforts to the Consortium protocols?

Have the PDs/PIs declared or expressed their intention to report any potential scientific or financial conflict of interest that may overlap with the clinical activities of the CPDPC?

Are the Ancillary Study (AS) concept, design and implementation, grounded on the PD(s)/PI(s) training and expertise and track record on implementing clinical studies (whether trial or observational)?

Have the PDs/PIs and key personnel demonstrated the capability to provide substantial scientific expertise that is consistent with and aligns with the objectives of the Consortium?

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?

In addition, for applications involving clinical trials

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:

Does the application propose new ways to enhance recruitment and retention of patients in all stages of the studied diseases?

Are any of the Ancillary Studies proposed novel for this field of research? Does it reinforce and expand the research objectives of the CPDPC?

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?

In addition, for applications involving clinical trials

Does the application 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:

Have the PDs/PIs shown how they will work in collaboration with the CDMC to implement procedures for uniform data collection, handling and transmittal of data, as well as data audits and other data quality control procedures, as established by the study protocol?

Have the PDs/PIs described their ability to recruit patients, procure specimens prospectively, collect epidemiological and clinical data using previously developed Common Data Elements, to contribute to the completion of one or several of the longitudinal clinical studies currently undergoing in the CPDPC ?

Has the applicant described the number of potential patients eligible for any of the longitudinal clinical studies, the CC is interested to participate in?

Have the applicant described the barriers and proposed solutions to fulfill the recruitment targets for each study of the studies they will participate?

For the NOD study: 1.- How well have the PDs/PIs assembled a multidisciplinary team with expertise in pancreatic cancer, diabetes, clinical research, early detection, and/or screening/surveillance? 2.- How have they demonstrated a commitment and the ability to recruit patients into the NOD study? 3.- Have they provided an estimate of the number of patients with NOD in their catchment area, demonstrated interaction with PCP’s in healthcare system and have IT support for future integration of a generic algorithm for identification of NOD patients into EMR in healthcare system?

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?

In addition, for applications involving clinical trials

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

Does the application 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 application 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?

Specific to this FOA:

Do(es) the PDs/PIs provided evidence of strong institutional support for the CC, including adequate space in which to conduct clinical and research activities and office space for staff. , Institutional resources for patient care and follow-up including personnel, space, and special laboratory facilities to contribute to the ongoing CPDPC ongoing clinical studies or to any of the AS they are proposing?

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

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

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) clinical samples ; 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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIDDK , in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC) and the National Cancer Advisory Board (NCAB).

. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that 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

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

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://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/NCI will have access to and may periodically review all data generated under an award. NIDDK/NCI staff may co-author publications of findings with awardees consistent with NIH and study policies.

8.Any third-party (including industry, academia, and foundations) collaboration should be governed by a research collaboration agreement (e.g. Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK/NCI policies and procedures, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network studies between grantee and third-party will be provided to the NIDDK and NCI Program staff and NIDDK and NCI Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK/NCI policies and network policies. Further, at the request of the NIDDK and NCI Program staff, any other network-relevant third-party agreements must be shared with NIDDK and NCI. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions , and Section 8.5.2, titled: Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support , noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award.

9. Any involvement of a third-party (including industry, academia, and foundations) in the study and network activities that includes access to any network study data and biosamples, or study results that are not publicly available, or using the name of the network or study or the name of the NIH or NIDDK or NCI, is permitted only after written permission by the NIDDK or NCI Program staff who will consult with others at NIH and NIDDK and NCI Technology Advancement Office

10. Study investigators are required 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 an individual company or other entity collaborating with the study. Any exception requires written approval from NIDDK/NCI Program staff.

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. Prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Central Repository to develop a Data Sharing Plan and 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, storage, and sharing 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 leadership 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, https://grants.nih.gov/policy/sharing.htm, 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.

13. Study investigators are required to comply with NIH Policy on the Dissemination of NIH Funded Clinical Trial Information as stated at https://grants.nih.gov/policy/clinical-trials/reporting/understanding/nih-policy.htm. Per policy, the awardee is responsible for meeting the expectations of this policy. Refer to additional information at https://grants.nih.gov/policy/clinical-trials/reporting/index.htm.

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

An NIDDK/NCI Project Scientists 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/NCI may designate additional NIDDK/NCI 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/NCI Project Scientists 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/NCI activities that may be relevant to the study to facilitate compatibility with the NIDDK/NCI 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/NCI. The NIDDK/NCI 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/NCI Project Scientists 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/NCI Project Scientists or Project Coordinator may be co-authors on study publications. In general, to warrant co-authorship, NIDDK/NCI 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/NCI.

4. Make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.

5. Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high-risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.

Areas of Joint Responsibility include:

In addition to the interactions defined above, NIDDK/NCI Projects 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/NCI Project Scientists. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK and NCI Project Scientists 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/NCI Project Scientists, will be selected by the NIDDK/NCI, 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/NCI 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/NCI member not voting), a second member selected by NIDDK/NCI, and the third member elected by the two prior selected members. These special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CR Part 16.

3. Reporting

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

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

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

Section VII. Agency Contacts

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

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

General Grants Information (Questions regarding application instructions, 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]

Jose Serrano M.D. Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8871
Email: [email protected]

Dana K. Andersen, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 410-868-0638
Email: [email protected]

Sudhir Srivastava, M.P.H., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7040
Email:[email protected]

Jo Ann Rinaudo, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7133
Email: [email protected]

Peter J. Kozel, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-4721
Email: [email protected]

Karin Johnson
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone:301-443-3603
[email protected]

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. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.