Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title
Limited Competition for the Continuation of Clinical Centers to Investigate the Pathogenesis, Etiology, and Treatment of Gastroparesis through the NIDDK Gastroparesis Consortium (U01 Clinical Trial Optional)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA-DK-16-010

Related Notices
None
Funding Opportunity Announcement (FOA) Number
RFA-DK-20-504
Companion Funding Opportunity

RFA-DK-20-505 - Limited Competition for the Continuation of the Scientific Data Research Center (SDRC) for the NIDDK Gastroparesis Consortium (U24 Clinical Trial Optional)

Number of Applications

Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.

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

93.847

Funding Opportunity Purpose

The primary purpose of this Limited Competition FOA is to invite applications from the clinical sites that have participated in the NIDDK Gastroparesis Clinical Research Consortium (GpCRC), to support the ongoing GpCRC cohorts, including the first U.S. registry of children and adolescents with gastroparesis, to support ongoing clinical trials and to provide a platform for informative ancillary studies. In addition, a major collaborative effort within the Consortium will be the establishment of an annotated repository of bio-specimens (blood stools and when feasible, gastric tissue) to allow for the identification and validation of biomarkers for risk stratification and/or early detection as well as to build on the ongoing Pathological Basis of gastroparesis study which will increase understanding of the pathological basis of gastroparesis.

Key Dates

Posted Date
September 24, 2020
Open Date (Earliest Submission Date)
November 16, 2020
Letter of Intent Due Date(s)

November 16, 2020

Application Due Date(s)

December 16, 2020

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February-March 2021

Advisory Council Review

May 2021

Earliest Start Date

July 2021

Expiration Date
December 17, 2020
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Gastroparesis (Gp) is a chronic, generally unremitting disease with improvement reported by not much more than about a quarter of patients after one year or more of follow up. From the cohort of GP patients, a higher proportion of women had gastroparesis of idiopathic etiology (69%) than men (46%). Women had more severe symptoms of stomach fullness, early satiety, postprandial fullness, bloating, a visible stomach and upper abdominal pain. Gastroparesis was associated with diabetes in a higher proportion of both non-Hispanic Blacks and Hispanics (about 60%) as compared with non-Hispanic Whites (28%). From this data, it was also demonstrated that non-Hispanic Blacks had more severe retching and vomiting and a higher percentage were hospitalized in the past year (66% vs 38%).Thus, the Gastroparesis Clinical Research Consortium(GpCRC) research team has clearly identified several factors that are associated with an adverse prognosis, including gender, age, race/ethnicity, putative viral illness at onset, depression overweight/obese habitus and disease outcome.

Initiated in 2006, the GpCRC is sponsored by the NIDDK to focus on the etiology, natural history, and therapy of gastroparesis. The goal of this Consortium continues to be the performance of clinical, epidemiological, and therapeutic research in gastroparesis and provide an infrastructure that can rapidly and efficiently design and conduct clinical trials for effective medical, surgical, or other interventions to improve treatment of patients with gastroparesis.

The GpCRC is a unique resource that has clearly demonstrated that the clinical burden of gastroparesis is significantly greater than previously realized and involves much more than the stomach. Through a series of registries totaling over 1000 patients at six clinical sites followed prospectively and systematically, and since 2015, due to increasing evidence that the pediatric age group was impacted with gastrointestinal dysfunction such as gastroparesis, the NIDDK invited the pediatric community to investigate these disorders along with the adult investigators given the absence of prospective pediatric gastroparesis studies.

This FOA invites collaborative U01 cooperative agreement applications from current awardees of the Gastroparesis Clinical Research Consortium (GpCRC) clinical centers to undertake continued follow-up of the GpCRC's Steering Committee approved studies. The clinical center applications submitted under this FOA will work collaboratively with the awardee(s) under RFA-DK-20-505 which will support the GpCR Scientific Data Research Center (SDRC).

Research Objectives

During the last funding cycle, the GpCRC has carefully provided a comprehensive understanding of the clinical spectrum, severity of symptoms, course and suffering imposed by gastroparesis and related disorders both in adults and in children. Through investigative efforts of the GpCRC, gastroparesis can be classified as a disease with distinct pathological and molecular profile. The primary objectives of the ongoing GpCRC are:

  • To continue to assess and study immune and other cell types isolated from gastroparesis patient samples at a single cell resolution. This may include studies of peripheral immune and epigenetic signatures in gastroparesis.
  • To evaluate disease modifying therapies instead of the standard approach of symptom management. Furthermore, based on our preliminary data that strongly suggest the same macrophage-driven immune dysregulation found in gastroparesis.
  • To incorporate endoscopic full thickness stomach biopsy techniques developed by the GpCRC investigators to bring a multi-omics approach to gastroparesis while carrying out the required clinical trials to show that they can modify and reverse the cellular and immune changes associated with gastroparesis and functional dyspepsia.
  • To build on the gains in the current pediatric registry for gastroparesis and functional dyspepsia by expanding the numbers of centers; evaluating the utility of non-scintigraphy methods for the diagnosis of pediatric gastroparesis; applying the Pediatric Quality of Life Inventory Gastroparesis Module (PQLGM) and determine the pediatric quality of life and response to gastroparesis therapies.
  • To continue to recruit and enroll patients in the ongoing clinical trial Buspirone for Early Satiety and Symptoms of Gastroparesis: A Multicenter, Randomized, Placebo-Controlled, Double-masked Trial (BESST). This is a multi-center, randomized, double-masked, placebo-controlled, parallel treatment groups phase 2 trial designed to determine whether buspirone, a 5-HT 1a receptor agonist, can improve early satiety and postprandial fullness in participants with symptoms of gastroparesis.
  • To continue to build on preliminary data on Dynamic antral contraction scintigraphy (DACS) for measurement of gastric motility during a conventional gastric emptying study as well as studies on Pyloric Sphincter Abnormalities in Patients with Gastroparesis Symptoms.
  • To recruit and enroll patients for the approved trial on Pyloric Sphincter abnormalities in Patients with Gastroparesis Symptoms using the FDA approved endoscopic functional luminal imaging probe (Endoflip) catheter which measures diameter, cross sectional area, pressure, compliance, distensibility of gastrointestinal muscle.
  • To develop Pragmatic trials for symptom relief targeting pathophysiology utilizing agents such as 5HT4 receptor agonists) and CGRP blockers.

As these objectives are accomplished, new directions to advance the understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis, can be developed by the GpCRC investigators thru collaborations with external investigators from several disciplines, including:

Immunologists: One of the overarching themes of discovery so far is that inflammation may play an important role in gastroparesis – either from diabetes, obesity, prior infection or surgery. The altered macrophage function may be a manifestation of an inflammatory “hit”. The addition of an immunologist would help focus this component of the work of the consortium.

Neurobiologist/Pain management specialists: Given the role of pain and nausea in the syndrome, what is the role of central versus peripheral causation?

Nutritionists: There has been no work yet focused on nutrition except for a comment about fermentable carbohydrates (FODMAPs). Given the evidence that FODMAPs may be important in IBS, this might deserve further investigation. Addition of a nutritionist would aid in investigations into the significant number of obese patients with gastroparesis.

Psychologists: The instruments include SF36, Beck and other measures of psychological distress. Results could be mined from existing data to develop hypotheses for future study.

Organization of the Gastroparesis Clinical Research Consortium (GpCRC)

The GpCRC will consist of the following entities: The NIDDK staff members (Project Scientist and Program Official, up to seven Clinical Centers (CCs), and one Scientific Data Research Center (SDRC), 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 Network are described in the Terms and Conditions of Award.

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

Study Group Components

1. Clinical Centers (CCs)

The Clinical Centers are responsible for developing and implementing all the clinical protocol and approved ancillary studies to be carried out by the GpCRC1. The CC will collect data in accordance with established study procedures and submit all samples and data to the Scientific Data Research Center (SDRC) and central laboratory and central reading centers, as appropriate and required by the protocol.

Investigators at the CCs will conduct analyses in conjunction with the SDRC. The study group will have exclusive access to data from the study population for a defined period, according to NIDDK and NIH data sharing policies. All study data are expected to be provided to the NIDDK Central Repository so that it can be shared as appropriate per NIDDK/NIH policy and consistent with achieving the goals of the program. The Steering Committee (see below) will establish policies under which ancillary studies may be conducted while the study is ongoing, consistent with applicable laws, regulations, and policies.

2. Scientific Data Research Center (SDRC)

There will be a single SDRC. The SDRC biostatisticians will work with the Clinical Center investigators to develop the scientific design of the study. The SDRC investigators will have primary responsibility for ensuring that the design of the study, including the primary outcome, is scientifically sound and is supported by appropriate power calculations. The SDRC will also provide biostatistical and analytic expertise and conduct analysis and interpretation of the laboratory and clinical data in conjunction with investigators at the Clinical Centers. The SDRC will be responsible for guiding development of the statistical analysis plan for the study as a whole and for each manuscript reporting pre-specified primary and secondary outcomes. The SDRC is will also be responsible for establishing all scientific collaborations for specialized outcomes measuring complications of diabetes and co-morbidities.

As part of its responsibility for establishing scientific collaborations, the SDRC will identify fixed and variable costs and establish procedures for negotiation of third-party agreements or selection of subcontractors (i.e. clinical sites, clinical/investigational pharmacies, clinical/research laboratories, drug distribution centers, biospecimen repositories, etc.), and develop processes to efficiently administer and manage same throughout the project. The NIDDK Technology Advancement Office must be consulted early in the process when an NIDDK-funded study enters into a collaboration agreement. These consults will be facilitated by the NIDDK Program Official.

In addition to these research functions, the SDRC is responsible for the collection, management and analysis of all clinical and laboratory data. The SDRC will continue to be responsible for ensuring subject confidentiality and safety, and quality control. The SDRC will conduct training and certification of study staff and maintain and update the manual of operations. The SDRC will continue to oversee implementation of and adherence to the study protocol. The SDRC will coordinate communication among and with the CCs.

The SDRC will also be responsible for establishing and managing activities related to the single IRB and will 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 SDRC will continue to be responsible for movement of biologic samples from the CCs to the central laboratory and, subsequently, to the NIDDK repository, where samples will be stored for future analysis. The SDRC will similarly continue to ensure the flow of radiographic tests and other collected data to the appropriate central reading center. The SDRC will also work with the NIDDK Central Data Repository to prepare all GPRC data for eventual archiving and distribution.

The SDRC will provide biostatistical, data management and analytic expertise. The SDRC will continue to prepare appropriately detailed reports to the Steering Committee and to the GpCRC DSMB, and to the NIDDK staff at regular intervals. The SDRC will be responsible for the planning and logistics of meetings of the Steering Committee and its subcommittees and will assist NIDDK with the logistics for DSMB meetings.

Study Governance

Steering Committee: The Steering Committee will be the main governing body of the SDRC (see the Terms and Conditions of Award). The Steering Committee will be composed of the Program Directors/Principal Investigators (PDs/PIs) of each CC in the Consortium, the PD/PI of the SDRC, the NIDDK Project Scientists and the NIDDK Program Official.

Study Co-Chairs will be appointed by NIDDK. The Steering Committee will have primary responsibility for the general organization of the GpCRC, and approval of 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 personnel will be held in the Washington, DC/Baltimore, MD metropolitan area or other suitable venue.

Executive Committee: An Executive Committee will be comprised of Study Co-Chairs (appointed by NIDDK), the PD/PI of the SDRC, the NIDDK Project Scientist and NIDDK Program Official.

The Chair of the Executive Committee will be appointed by the NIDDK. 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 and SDRC 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 and ad hoc members from other NIH institutes, as necessary, 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 continuation of each study. The DSMB will be responsible for final approval of the Data and Safety Monitoring Plan developed by the SDRC. All protocols or changes to protocols will be approved by Institutional Review Boards, the Steering Committee, the Data and Safety Monitoring Board, and the NIDDK before initiation.

Other Special Performance Requirements:

The GpCRC will continue to be a collaborative effort that will require frequent interactions of awardees among themselves and with the NIDDK. Applicants are expected to:

  • Participate in Steering Committee meetings (expected to occur in person 3-4 times a year in the Washington DC/Baltimore,MD, metropolitan areas or other suitable venue), and as monthly (or as needed) teleconference, site visits as required by the NIDDK 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 GpCRC;
  • 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 that the site is selected for participation; Comply with all study policies and quality assurance measures approved by the Steering Committee;
  • 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 (Clinical Centers and subsites only);
  • Report all adverse events in accordance with procedures established by the Steering Committee, and NIDDK and Food and Drug Administration (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; 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

Funding Instrument

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

Application Types Allowed
Renewal

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?
Optional: Accepting applications that either propose or do not propose clinical trial(s)

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $3.0 million in FY 2021 to fund 7 awards.

Award Budget

Application budgets are limited to $250,000 in direct costs per year. Application budgets should reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

 This FOA is limited to the current awardees of the NIDDK Gastroparesis Consortium under RFA-DK-16-010.

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
Foreign Institutions

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

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

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

Required Registrations

Applicant organizations

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

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number 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.

Eligible Individuals (Program Director/Principal Investigator)

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

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

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

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

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: NIDDKLetterofIntent@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

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.

SUPPLEMENTAL INSTRUCTIONS FOR CLINICAL CENTERS (CC):

Applications for the CCs will be assessed upon their clinical capacity to recruit, enroll, and retain patients in clinical studies and the investigators’ knowledge and expertise in the diagnosis and management of acute pancreatitis and diabetes and their complications. The CC application (including subcontract sites) must demonstrate how investigators will be able to submit data to the SDRC and biospecimens to the NIDDK Central Repository (supported by an independent contract from NIDDK) and to central laboratories and biological cores as approved by the Steering Committee. CCs must show how they will work in collaboration with the SDRC 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 must 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.

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 approved protocols. Each CC application may consider the addition of other scientific personnel who must be fully justified.

The additional scientific 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 based upon network objectives and the availability of support. The PD/PI should state his/her general support of collaborative research and interaction with the NIDDK, the other CCs, and the SDRC through the Network concept.

Future clinical study protocols will be overseen by a centralized IRB. Investigators are encouraged to express their agreement with this model or comment on barriers to implementation of centralized IRB review and ongoing oversight at their individual institutions.

In order to maximize the impact and efficiency of the consortium, investigators are requested to state their willingness to present site-specific studies that may potentially conflict with the activities of the GPCRC to the Steering Committee for comment and consideration as network-wide studies.

SF424(R&R) Senior/Key Person Profile

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

All proposed key personnel must demonstrate the capability to provide substantial scientific expertise that is consistent with and aligns with the objectives of the GPCRC. The final decision on the acceptance of the additional scientific personnel will be at the discretion of the NIDDK 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, the other CCs, and the SDRC as described in the collaborative agreement.

R&R or Modular Budget

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

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.  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.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

The applicant should consider the objectives described in Section I (“Funding Opportunity Description. Research Objectives”) and in responding to this RFA, the Research Strategy section should include:

  • A discussion of the significance of the problem being studied, the need for the study, and the potential impact of the results of the study, as well as how the study will test the hypothesis(es) proposed.
  • A description of and rationale for the proposed study design;
  • A discussion of progress made during previous funding periods; A concise description of the overall strategy, methodology and analyses to be used to accomplish the goals and specific aims of the study;
  • A description of the protocol(s) to be followed, including a discussion of potential biases or challenges in the protocol and how they will be addressed. Applications should discuss (1) exclusion and inclusion criteria for selecting samples as cases or controls; and (2) discuss procedures for acquiring samples and obtaining clearances from State and regulatory authorities, including those from an institutional review board (IRB).
  • A brief acknowledgement of responsibilities as part of a multi-center, collaborative project.

In this section, there should be sufficient description of the items listed above to permit thorough evaluation of the proposed study.

The Clinical Center (CC) PD/PI should describe willingness to work collaboratively with other members of the Consortium, the Scientific Data Research Center (SDRC), the Data Safety Monitoring Board and the NIDDK Central repository. CC applicants (including subcontract sites) should describe how they will be able to submit data to the SDRC and biospecimens to the NIDDK Central Repository (supported by an independent contract from NIDDK) and to central laboratories and biological cores as approved by the Steering Committee. CCs must show how they will work in collaboration with the SDRC 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 must 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.

In addition, the applicants for Clinical Centers must propose protocols to be carried out by the consortium.

Applicants must include descriptions of any plans for interacting with potential private sector collaborators.

Applicants must document the ability to recruit patients, procure specimens prospectively, collect epidemiological and clinical data using previously developed Common Data Elements, and to process, track, and store specimens. Applicants should describe in detail any proposed retrospective and/or prospective specimen collections that will be used for Consortium activities. The description should include information on the types of patients and control subjects to be accrued, clinical information to be collected, and types of specimens to be collected.

An organizational structure for the CC should be set forth in the application, delineating specific personnel (e.g., pathologists, radiologists, neurobiologist, nutritionists, etc.) available to carry out the approved protocols. The PD/PI should state his/her general support of collaborative research and interaction with the NIDDK, the other CCs, and the SDRC through the Network concept.

If feasible, future clinical study protocols may be overseen by a centralized IRB. Investigators are encouraged to express willingness to consider this model or comment on barriers to implementation of centralized IRB review and ongoing oversight at their individual institutions. In order to maximize the impact and efficiency of the GpCRC, investigators are requested to state willingness to present site-specific gastroparesis studies that may potentially conflict with the activities of the Consortium to the Steering Committee for comment and consideration as network-wide studies.

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.

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

The following modifications also apply:

 

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data and Resource (Biological Sample) Sharing Plan.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving 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.

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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.

Overall Impact

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

Scored Review Criteria

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

Significance

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

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:

 

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 GpCRC?

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?

Do the additional scientific personnel provide unique expertise that is suited to the scientific mission of the GpCRC? Have the additional scientific personnel demonstrated an ongoing record of scientific accomplishments that are aligned with the GpCRC scientific objectives?

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?

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 sufficiently demonstrated how they will work in collaboration with the SDRC 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 thoroughly described their ability to recruit patients, procure specimens prospectively, collect epidemiological and clinical data using previously developed Common Data Elements, to contribute to the longitudinal clinical studies planned by the GpCRC as described in PHS 398 Research Plan of this FOA?

Has the applicant described in sufficient detail the number of potential patients eligible for a longitudinal clinical study of Gastroparesis?

Has the applicant concretely described the barriers and proposed effective solutions to fulfill the recruitment targets?

Future patient enrollment potential: Are the CC patient recruitment, enrollment, and retention plans sufficient to contribute to the long term follow up of patients? Is there an appropriate and feasible strategy to optimize retention and follow-up of patients enrolled in the GpCRC registry?

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:

Does the PD(s)/PI(s) provide 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 proposed GPCRC longitudinal study or to any of the ancillary studies they are proposing?

Additional Review Criteria

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

Specific to applications involving clinical trials

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

Additional Review Considerations

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

Applications from Foreign Organizations

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

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 will receive a written critique.

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.

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. 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.

 

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 https://grants.nih.gov/policy/humansubjects.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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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. 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.

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.

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.

Cooperative Agreement Terms and Conditions of Award

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

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

The PD(s)/PI(s) will 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 NIDDK 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 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 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 Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and network policies. Further, at the request of the NIDDK Program staff, any other network-relevant third-party agreements must be shared with NIDDK. 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, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK 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 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 https://www.niddk.nih.gov/-/media/Files/Research-Funding/Process/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 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 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 mission 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:

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.

Review and approve protocols prior to implementation to insure they are within the scope of peer review, for safety considerations, as required by Federal regulations.

The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.

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

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

Areas of Joint Responsibility include:

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

Steering Committee

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

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

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

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

Dispute Resolution

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten 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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

Frank A. Hamilton, M.D., MPH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8877
Email:hamiltonf@mail.nih.gov


Jose Serrano, M.D., Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8871
Email: jose.serrano@nih.gov

Peer Review Contact(s)

Elena Sanovich, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8886
Email: sanoviche@mail.nih.gov

Financial/Grants Management Contact(s)

Ms. Beth Gutierrez
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8844
Email: gutierrezel@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.