Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization.

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

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Parkinson’s disease (PD) is a multisystem disorder associated with a heterogeneity of clinical changes, suggesting the existence of different subtypes, characterized by both motor and non-motor dysfunctions. There has been a longstanding interest in the neurological symptoms of PD, but disease symptoms are not limited to motor dysfunction. More than 50% of patients who develop PD often have a history of complaints affecting nearly all parts of the gastrointestinal (GI) system including the esophagus (dysphagia), stomach (nausea, gastroparesis), and colon (constipation), as well as the rectum and anus (anorectal/defecatory dysfunction). The fact that GI symptoms may be present years before the appearance of motor symptoms (prodromal phase) gave rise to the hypothesis that the gut plays a key, but undefined, role in the initiation and/or progression of PD and that the gut may be an unexplored diagnostic and/or therapeutic target. Elucidation of the mechanisms underlying the role of the GI tract in pathogenesis of PD remains a major challenge.

There is also increasing recognition that gut health has a significant impact on brain morphology and function. Prodromal GI dysfunction in PD has been linked to dysbiosis, enteric inflammation, enteric infection, and/or exposure to environmental toxicants. Solid evidence supports a close association among inflammation, neuroimmune interactions, and PD disease progression, and retrospective studies suggest an increased risk of PD in patients with inflammatory GI pathologies. For example, differences in gut microbiota in PD patients have been linked to brain neurodegeneration and correlated with severity and duration of motor symptoms. Thus, the therapeutic potential of targeting the prodromal phase of PD requires identification of the key gut-brain pathways and gut-derived biomarkers that can be leveraged to develop mechanism-based diagnostic tools as well as therapies that impact disease progression in PD.

Progress in the area of gut-brain interactions in PD requires a framework to support a multidisciplinary approach between investigators in neurology and gastroenterology. Research into the temporal relationship between GI symptoms and disease progression in PD needs large cross-sectional and longitudinal collections of patient data and biospecimens, but few centers have sufficient information on GI dysfunction in patients with PD. Thus, critical to success of this initiative is the collection of data and samples under a large-scale data sharing effort starting from the prodromal non-motor GI phase to the overt motor phase. Standardized biological samples and phenotypic data collected from clinical research are rich resources for translational research to identify and validate novel and high-quality biomarkers that will accelerate the discovery of new drugs and targets, facilitate risk stratification for clinical trials, and provide predictive diagnostics and treatment responses for personalized medicine. A multidisciplinary collaborative effort will provide the infrastructure needed to establish an annotated repository of participant biospecimens (e.g., blood, stool, and GI tissues) needed to overcome the practical hurdles that have precluded development of novel interventions based on gut-based targets that may be applicable to PD and potentially to the broader spectrum of neurodegenerative diseases.

The field would also benefit from application of new technologies. Integrated data from advanced techniques in brain imaging, brain-gut neuroimaging, and assessment of autonomic dysfunction could be used to investigate the role of the gut in the pathogenesis of PD as well as the mechanisms associated with progressive neurodegeneration along the gut-brain axis. Current and developing technologies that allow repeated non-invasive sampling of luminal contents along the length of the gut in humans could be leveraged to study the microbiota or its products. Use of state-of-the-art scalable computational and analytical methodologies may allow integration (conceptual/statistical) of meta-organism multi-omic data with other data constructs. Advanced molecular methods for identification of single cell genomics, transcriptomics, proteomics, or cite-sequencing of surface proteins can provide insights regarding the role of specific cells in the gut in disease pathogenesis.

Research Objectives

The goal of this Notice of Funding Opportunity (NOFO) is to enhance our understanding of the temporal onset of GI symptoms in PD and changes in gut-brain communication that can be used to leverage the potential role of the GI tract in the pathogenesis and progress of PD and to improve patient diagnosis, care, and outcomes. To achieve this objective, two different types of centers will form a consortium. This NOFO invites cooperative agreement applications for multiple Gastroenterology Neurology Research Centers (GNRC) that would work together with a biospecimen repository and Coordinating and Data Management Center (CDMC) described in the companion NOFO, RFA-DK-23-001. Although a CDMC and GNRC may exist at the same institution, the two types of centers require separate applications, and these will be evaluated independently by the criteria outlined below. The CDMC and GNRCs will work together cooperatively as a Consortium (GBPDC) to address these research objectives: 1) to collect prospective cross-sectional and longitudinal participant biospecimens with temporally coordinated evaluations of GI and neurological functions to better characterize the phenotype of PD patients with, versus those without, GI symptoms; 2) to elucidate the biological processes and pathways relevant to the role of the GI tract in pathogenesis and progress of PD with regard to disease heterogeneity or severity; 3) to characterize GI symptoms, pathology, and gut-brain communication in PD to detect early and longitudinal changes in gut function and activity that correspond to the development or progression of PD motor symptoms; 4) to identify possible novel gut-based functional/ molecular/other biomarkers, diagnostic tools, and therapeutic targets; and 5) to investigate the impact of neuroimmune interactions in the GI tract on gut-brain communication and PD risk. Studies should focus on PD patients with and without overt GI symptoms and may include patients with GI pathologies (e.g., genetic markers, like LRRK2, associated with PD and chronic GI inflammation) who may be at higher risk for PD. Studies must have age-matched healthy controls. Participant enrollment targets should be supported by documentation of institutional availability, include recruitment and retention strategies that may be specific to the target population, and be sufficient to power the proposed functional and molecular analyses. While participant enrollment and sample collection and analyses are critical components of the consortium, applications should also include pathobiological mechanism-based objectives. Projects submitted to this NOFO should include expertise in both areas of clinical gastroenterology and clinical neurology with documented accomplishments in their field. A previous or ongoing collaboration or record of collaboration is not required.

Specific Areas of Research Interest

Areas of research interest include, but are not limited to:

• Prospective recruitment and phenotypic evaluation of PD patients that consider the heterogeneity of the disease with regard to occurrence of prodromal GI dysfunction, symptom onset, and disease progression to generate a multi-sample repository of participant biosamples and clinical data. Analyses may include environmental exposure data collection for the identification of known (e.g., alpha-synuclein) or putative GI-based or circulating biomarkers; changes in specific populations of enteric neurons, particularly as they relate to autonomic function or CNS neuronal function; alterations in the GI microbiome or microbial metabolites; or other molecular mechanisms that predict or contraindicate patient stratification, correlate with specific symptoms of prodromal GI dysfunction, or associate with disease severity in PD.
• Prospective participant recruitment and evaluation for longitudinal studies of temporal, region-specific, cellular, molecular, or other changes in the GI tract in PD that correspond to onset or progression of GI symptoms, altered gut-brain communication, evolution and/or progression of motor symptoms. These studies should have multipoint time sampling (e.g., blood, stool, biopsy tissue) and protocols will be harmonized across the GBPDC. The timing and number of samples collected each year should be consistent with the proposed GI- and neurology-based objectives.
• Participant analyses should be complemented by focused mechanistic studies using participant biospecimens that may be designed in parallel with animal models of PD, in-vitro, or other experimental (e.g., induced pluripotent stem cells) systems. These studies should provide clinically relevant mechanistic insights by leveraging state-of-the-art technologies to perform functional, imaging, molecular, or multi-omic assessments including multi-modal single-cell analyses, Cite-seq for cell immunotyping, or other specialized techniques as required by specific projects.
• Multi-omic analyses of the composition and activities of the intestinal microbiome in participants to identify relationships between microbiome composition and the phenotype, onset, duration, risk and severity of GI dysfunction in PD.
• Pilot analyses of pre-existing clinical data and biological samples from within and beyond the GNRC, either by request or through collaboration, to determine changes in GI function, gut-brain molecular pathways, gut biomarkers, or other factors that predict the course of PD. This could involve integration of multi-level datasets and/or use of novel molecular or multi-omic approaches to identify and characterize differences in the GI tract of PD patients that predict onset or existence of GI symptoms, disease progression or severity, sensory or motor function in gut-brain communication and would be leveraged to inform longitudinal studies.
• Application of novel technologies such as scalable multi-omic tools for data analyses and integration; assessment of gut brain bidirectional communication in PD patients through advanced neuroimaging of brain and gut or tests of autonomic function; studies that integrate enteric nervous system function, epithelial cell biology, and mucosal immunology in PD patients. If neuroimaging is proposed as part of the study, imaging protocols should match those followed by the Alzheimer’s Disease Neuroimaging Initiative (https://adni.loni.usc.edu/methods/) as closely as possible and also meet the requirements set by NIDDK Central Repository (NIDDK-CR).
• Connections or interactions between dopaminergic or other relevant neurotransmitter circuitry in the brain and the corresponding circuitry in the gut and the initiation or progression of motor or non-motor symptoms.

Organization and Management of the Gastroenterology Neurology Research Centers (GNRC) of the Gut-Brain Communication in Parkinson’s Disease Consortium (GBPDC)

The NIDDK IBDGC will consist of up to five Gastroenterology Neurology Research Centers (GNRC) and one Coordinating and Data Management Center (CDMC). This NOFO invites applications for the GNRC components of the GBPDC. The CDMC is fully described in the companion NOFO, RFA-DK-23-001. Applicants are strongly encouraged to form a multidisciplinary team of investigators (e.g., clinical and research gastroenterologists, clinical and research neurologists, enteric neurobiologist, neuroscientists, computational scientists, etc. as appropriate) and additional necessary personnel, such as a research coordinator and staff research associates. Applicants may also establish additional collaborations to ensure inclusion of appropriate expertise in the use of the proposed clinical and experimental techniques and analytical methods.

This program also encourages applications that would support diverse teams of investigators, including team members that are underrepresented in the biomedical, behavioral, or clinical research workforce. Such individuals include but are not limited to those from underrepresented racial and ethnic groups, those with disabilities, and those from disadvantaged backgrounds. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. Please see NOT-OD-20-031 for details.

Each GNRC will be actively involved in the recruitment and evaluation of PD patients and age-matched controls. GNRC may include one or more institutions in order to conduct center-specific studies that take advantage of the experience and expertise in the diagnosis, management, and care of PD patients. The GNRCs will recruit participants into the study and conduct phenotypic evaluations, cross-sectional, and longitudinal follow-up of these subjects. Inclusion and exclusion criteria for PD subject enrollment must be clearly defined, and the applicant must describe how many follow-up visits are expected. All applicants are encouraged to consider strategies that include recruitment and inclusion of individuals from diverse populations. .

The GNRCs may collect a variety of biological samples from participants (e.g., cerebrospinal fluid (CSF), saliva, stool, blood, plasma, serum, intestinal biopsies). Collection of biological specimens should conform to the specimen collection protocols of the NIDDK-CR (https://repository.niddk.nih.gov/pages/for_submitters/) and NINDS BioSEND Repository (https://biosend.org/expertise.html). Applicants are required to collect blood for DNA at the initial visit, and to collect blood for RNA, serum, and plasma annually. Where applicable, applicants will be expected to collect CSF and GI biopsies at least once and are strongly encouraged to collect these samples annually. Costs for biospecimen kits, processing, and storage must be included in the application budget, and applicants are advised to contact the NIDDK ([email protected] or [email protected]) Repository staff for a quote. As an alternative, the GBPDC may subcontract biospecimen processing to a commercial provider of these services if needed. Applicants will be required to collect standard GBPDC clinical assessments for PD subjects (e.g., https://pdbp.ninds.nih.gov/researcher/clinical-assessments#lewy-body-dementia-forms) and should budget for any assessments they may need to purchase. Additional clinical, imaging, and/or biospecimen measures may be proposed if needed and justified, and the applicant should provide details on collection methods, protocols and whether these additional assessments will be shareable through the GBPDC or through other repositories. Applicants proposing to use induced pluripotent stem cells (IPSC) line derivation should include an appropriate budget for these studies.

The GNRCs will be expected to conduct independent analyses (enlisting support from the CDMC, as appropriate), to participate in collaborative projects with other GNRCs, and to allocate resources and personnel for the performance of both independent and collaborative studies. GNRCs will be expected to share data and participant specimens with other GBPDC centers, as appropriate and consistent with program goals. In addition, all applications must follow GBPDC protocols for data and biospecimen collection in subjects with PD and controls. NIDDK-CR requires Limited Data Sets devoid of direct identifiers and not considered fully de-identified (https://privacyruleandresearch.nih.gov/pr_08.asp). GNRCs must work in concert with the CDMC to implement procedures for uniform data collection, handling and transmittal, as well as data audits and other data quality control procedures, as determined by the study protocol to include establishment of a single IRB and Global Unique Identifier (GUID) solution for participant data management. GUIDs are required for each GNRC participant and the NIDDK has joined the NIH-centralized GUID server for participant data management across institutes and studies. The GUID allows data to be associated with a research participant without exposing or transferring personally identifiable information (PII) and/or protected health information (PHI). GNRCs will transmit phenotypic, genetic, microbiome, and other data to databases maintained by the CDMC (described in the companion NOFO, RFA-DK-23-001).

Annual milestones should be included in the application. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should address timely subject recruitment and complete/accurate data and biospecimen submission. These awards will be managed as cooperative agreements and funding of non-competing award years will depend on milestone accomplishment. Projects that do not comply with terms, conditions, and established milestones of the award and of this program may be terminated early.

GNRC members will staff the operational committees of the GBPDC (e.g., Steering Recruitment, Phenotyping, Analysis, etc.), thereby collaborating on the design of joint projects and the establishment of uniform procedures and policies.

Steering committee (see also section VI): The Steering Committee of the GBPDC will be responsible for all operational decisions, which will be binding upon all members of the GBPDC. The Steering Committee has the primary responsibility for implementing the objectives of the GBPDC, including identifying areas of potential research, developing and implementing common protocols, and analyzing and publishing study results. The frequency of the Steering Committee meetings will be established at the first meeting but is expected to meet 4 times per year with monthly videoconferences. All Steering Committee members or their designees are expected to attend these meetings. At least two meetings per year are expected to be face-to-face (weather and public health issues permitting), usually in the Washington, DC metro area, and GBPDC PIs and coordinators are expected to attend the quarterly meetings. The Steering Committee may create subcommittees to manage specific functions such as protocol development or publications. The CDMC will manage the operations of the GBPDC Steering Committee and other operational committees and provide the infrastructure for the efficient design and conduct of multicenter clinical studies and establish a repository of participant samples that may be used for ancillary studies. The voting members of Steering Committee consist of:

• PIs from each GNRC (one vote per center; multi-PI applications are allowed, but each awarded Center will only get one vote on the Steering Committee)
• PI from the CDMC Data Coordinating Center
• NIDDK Project Scientist
• Steering Committee chairperson, other than the NIDDK Project Scientist, will be appointed by the Steering committee in consultation with the NIDDK Program Official.

Applications Not Supported by this NOFO

Applications including the following types of studies will be considered non-responsive to this NOFO:

• Applications which do not include recruitment and phenotyping of human PD subjects and age-matched controls.
• Applications focused exclusively on animal models or in-vitro studies.
• Applications containing a clinical trial.
• Applications that do not include plans for prospective longitudinal collection of clinical data and biosamples.
• Applications that focus exclusively on neurology or gastroenterology patients.

Nonresponsive applications will not be reviewed.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; 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 SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

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

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

The PD(s)/PI(s) will be each required to declare a minimum effort of 1.8 calendar-months (15 percent) effort each per year for first year and 1.2 calendar months (10%) thereafter. Applications proposing Multiple PD(s)/PIs(s) must have a minimum combined PD/PI effort of 1.8 person months for each year, and the role of each PD/PI should be clearly defined. Applications that do not propose this minimum effort will be withdrawn and will not be reviewed.

All applicable costs must be anticipated, budgeted, and justified by the applicant; the NIDDK will not provide supplemental funds to cover costs for biospecimen and data collection

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: In the description and explanation of the research strategy, address specifically the following points:

• Describe the range of interdisciplinary expertise available to ensure the success of proposed project. .
• Plans for prioritizing the longitudinal recruitment of participants with PD with and without GI symptoms with appropriate rationale for the choice of subject populations, both those already diagnosed with PD and those at elevated risk of PD.
• How the proposed studies and any innovative approaches for participant recruitment, biospecimen procurement or analysis, or for monitoring subjects for the development, progression, or severity of disease in PD will reduce the impediments to studying gut-brain based mechanisms across the entire timeline of PD from the prodromal phase and throughout the ultimate clinical course.
• Acknowledgment that clinical assessments and biospecimen collection will occur as required in GBPDC protocols.
• How the proposed studies will improve our understanding of the role of the gut in the pathogenesis of PD and the specific processes/mechanisms that link GI symptoms and PD motor dysfunction.
• Rationale and plans for any use of preexisting biospecimens or data.
• Rationale for any inclusion of studies involving animal, in vitro, or other experimental models (e.g., IPSC) and how they complement proposed clinical analyses.

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.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Policy. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• All investigators funded under this NOFO will be expected to share their data publicly through a web-based platform that is easy to access and readily transferable (e.g., REDCap) or other public portals approved by NIDDK. Therefore, the Data Management and Sharing Plan should include a summary of how the applicant will manage data submission and interactions with the platform or other NIDDK approved public portal.
• Regardless of the amount of direct costs requested for any one year, applicants are expected to refer to the Implementation Details for the NIH Data Management and Sharing Policy notification (NOT-OD-22-189) and related announcements. Concerns, governances, policies, and procedures set forth in this notice around data collection, integrity, storage, security, etc. should be addressed in the application. NIH has issued a Data Management and Sharing notification (NOT-OD-22-189) and applications in response to this NOFO should be responsive to this notification.
• Specifically, consistent with achieving the objectives of the GBPDC, all resources, tools, technologies, protocols (including analytical methods), and other research resources are expected to be made publicly available to the larger national research community.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier 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 the National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Use of Common Data Elements in NIH-funded Research

NIDDK requests 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) Repository (https://cde.nlm.nih.gov) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The CDE Repository 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 CDE Repository 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

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.

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

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

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Diabetes and Digestive and Kidney Disorders (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 NOFO.

Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Disorders Advisory Council (NDDKDAC). 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 2.4.4 Disposition of Applications.

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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, Recipients, and Activities, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. 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 https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/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 NOFO.

• For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 (HHS) grant administration regulations at 45 CFR Part 75 and 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and 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). Recipient(s) will name investigators to serve as members on a Steering Committee and other subcommittees, as appropriate, meeting periodically. Recipients 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 recipient/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, completeness, and security. Recipients 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 recipients/sites. Such reports are in addition to the required annual noncompeting continuation progress report.

7. Reporting of the study findings. Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. The recipient 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 recipients consistent with NIH and study policies.

8. Any third-party collaboration (including but not limited to interactions with organizations from industry, academia, and nonprofit institutions) 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 but not limited to industry, academia, and nonprofit institutions) in the study and network activities that includes access to any network generated resources (i.e., data and bio-samples), 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. Maintaining confidentiality of information: The recipient(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.

11. Data Management and Sharing Plan: In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. By the end of the funding or proprietary period, a recipient or study group may not continue to use or share study generated resources until those resources are available to the public via a NIDDK approved repository per the NIDDK approved plan. The NIDDK has established a Central Repository to support the receipt, storage, and distribution of data, bio-samples, and other resources generated in clinical studies funded by the NIH/NIDDK. When the NIDDK Central Repository is to be utilized, prior to enrolling participants, the PI or his/her designee will coordinate with the NIDDK Program and Central Repository staff to prepare for eventual archiving and distribution of the study generated resources that are to be maintained in the Central Repository. These resources will be available to the wider scientific community in accordance with the NIH Data Management and Sharing policy (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), per the NIDDK approved data management and sharing plan.

12. Study investigators are required to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols, steering committee policies on publications, and the NIDDK approved sharing plan.

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 recipient 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 Scientist with substantial involvement will:

1. Serve as the contact point for all facets of the scientific interaction with the recipient (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the recipient 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 recipients to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

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

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

4. Have substantial involvement assisting in the design and coordination of research activities for recipients 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 recipients by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results.

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

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

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

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

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

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

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

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

Areas of Joint Responsibility include:

In addition to the interactions defined above, NIDDK Project Scientist and Recipients 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 recipients, 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. The NIDDK Program Official may serve as a non-voting member on the SC.

A Chairperson of the Steering Committee will be selected and voted on by the Steering Committee members. The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation. The NIDDK Project Scientist may not serve as Chairperson. The NIDDK Program Official should be consulted regarding the selection of the Chairperson to provide any feedback regarding concerns regarding potential for bias or conflict of interest or lack of required expertise.

External Consultants

An independent panel of External Consultants may be established by the Steering Committee. The External Experts will review periodically interim progress of the U01s and report to the Steering Committee members. Members of the panel of External Experts may be asked, on an ad hoc basis, to participate in the peer review of applications for new research initiatives that utilize special opportunity pool funds.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients 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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Terez Shea-Donohue, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301 825-2314
Email: [email protected]

Maria Davila-Bloom, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7637
Email: [email protected]

Angela Walters
National Institute of Diabetes and Digestive and Kidney Disorders (NIDDK)
Telephone: 301-435-6950
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.