National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
U01 Research Project – Cooperative Agreements
Only one application per institution is allowed, as defined in Part 2, Section III. 3. Additional Information on Eligibility
This is a Notice of Funding Opportunity (NOFO) for a Limited Competition that will invite applications from eligible organizations to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the applications will be peer-reviewed, and only meritorious applications will be considered.
The goals of the Liver Cirrhosis Network will be to complete enrollment in the Liver Cirrhosis Network Cohort; and in the Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States clinical studies.
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS - New/Renewal/Resubmission/Revision, as allowed | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| Not Applicable | March 06, 2026 | Not Applicable | July 2026 | October 2026 | December 2026 |
| Not Applicable | March 08, 2027 | Not Applicable | July 2027 | October 2027 | December 2027 |
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).
Not Applicable
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.
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.
Purpose:
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is proposing the continuation of the Liver Cirrhosis Network through this Limited Competition Notice of Funding Opportunity Announcement which is renewing the LCN Clinical Centers awarded under RFA-DK-20-003. Please see Section III. Eligibility for additional information.In conjunction with RFA-DK-26-309 NIDDK is renewing the LCN Scientific Data Coordination Center, to continue the long-term follow-up of patients enrolled in the LCN Cohort Study; and to complete enrollment and the two years of treatment and follow up of patients the LCN RESCU trials.In accordance with NIH standard peer-review processes, the applications will be peer-reviewed, and only meritorious applications will be considered.
Background:
Cirrhosis represents not a single disease, but rather the outcome of many chronic liver diseases, caused by a wide range of conditions. The etiologies of cirrhosis in the United States include infectious causes such as chronic hepatitis B, C and D; genetic causes such as Wilson disease, hemochromatosis and alpha-1-antitrypsin deficiency; nutritional or metabolic causes such as nonalcoholic steatohepatitis (NASH also known as metabolic dysfunction associated steatohepatitis; MASH); autoimmunity such as autoimmune hepatitis, primary biliary cirrhosis and sclerosing cholangitis; and toxic causes such as alcoholic liver disease, and chronic liver injury from medications such as methotrexate and amiodarone. Cirrhosis from these diseases is almost always the result of chronic injury with persistent inflammation and cell damage that results in faulty healing and fibrosis. As fibrosis accumulates it causes distortion of the architecture of liver, portal hypertension, and compromise of liver function. Clinical complications of cirrhosis include symptoms (such as fatigue, weakness, weight loss, itching and jaundice), gastrointestinal bleeding from varices or portal hypertensive gastropathy, ascites and disturbance of fluid and electrolyte balance, renal dysfunction, and hepatic encephalopathy. The most dreaded complication of cirrhosis is hepatocellular carcinoma, a highly fatal cancer that arises in 1 to 3% of persons with cirrhosis yearly. Once cirrhosis is present, treatment of the underlying liver disease can slow or stop further progress, but it does not eliminate all risk of complications.
Mortality due to liver disease remains a significant public health burden in the United States, currently ranked as the 10th most common cause of death overall, and ranking 6th in persons below the age of 65 years. The prevalence of cirrhosis appears to be rising in some populations, such as persons living with HIV infection, genetic immune deficiency disorders, and cystic fibrosis. Hepatocellular carcinoma incidence is also rising in the United States and is a surrogate for the prevalence of cirrhosis.
Treatment of underlying chronic liver disease such as with antivirals for chronic hepatitis B and C; therapeutic phlebotomy for genetic hemochromatosis; ursodiol for primary biliary cirrhosis; weight loss for nonalcoholic steatohepatitis, and cessation of alcohol consumption for alcoholic liver disease, all are primarily aimed at prevention of cirrhosis by early abrogation of ongoing injury to the still noncirrhotic liver. Curing or ameliorating the liver disease may allow the injured liver to invoke endogenous mechanisms to reverse the consequences of chronic inflammation and the accumulation of mild or even moderate amounts of liver fibrosis. However, once cirrhosis has been established, neutralization of the causes of liver disease generally will not reverse the cirrhosis.
Liver transplantation is currently the only medically viable avenue for patients with cirrhosis and end-stage liver disease that will extend longevity. On an annual basis, despite treatment success rates for chronic hepatitis C and other liver diseases, the number of liver transplants done in the United States continues to increase, most recently rising above 10,000 per year. Of patients placed on the waiting list, at least 3000 patients become too ill to undergo transplantation or die while waiting for an organ each year. However, it is important to emphasize that liver transplantation is an option for only 10% to20% of patients with end-stage liver disease and that the death rates from chronic liver disease and cirrhosis is more than 50,000 each year in the United States. This rate includes persons who were never placed upon a liver transplant list because they had comorbid conditions that did not allow transplant surgery or had social, psychological, or financial reasons for not qualifying for this serious and expensive option.
Given the discrepancy between the demand and the supply of organs for patients on liver transplant waiting lists and the even more numerous patients who are unable to be considered for listing for liver transplantation, there is a significant need to improve our understanding of clinical and translational scientific aspects of liver fibrosis and cirrhosis. This includes improving the understanding of the underlying pro- and anti-fibrotic mechanisms as well as risk factors that accentuate pro- and anti-fibrotic processes and how can this knowledge improve clinical practice and the prevention of the serious complications of cirrhosis.
To address the public health burden of liver cirrhosis, the NIDDK established the Liver Cirrhosis Network (LCN) through RFA DK-20-003 and RFA DK-20-004. The LCN subsequently conceived, developed and operationalized the Liver Cirrhosis Network Cohort Study (LCN Cohort NCT05740358) a prospective study of the natural history of compensated cirrhosis due to its many known causes; and the Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States (LCN RESCU NCT05832229) a randomized, double-blind, placebo-controlled Phase 2 clinical trial of rosuvastatin in patients with compensated cirrhosis due to its major causes. The LCN Cohort Study is nearing the enrollment objective of 1200 participants while the LCN RESCU study has enrolled one third of the target enrollment.
Objectives:
Clinical Center applications in response to this Notice of Funding Opportunity are charged with the enhancing patient recruitment and retention to complete the research goals in the LCN Cohort Study and RESCU Trial. The central and critical objective of this NOFO is to promote clinical and translational research on cirrhosis that might lead to means of treatment, amelioration, and possible reversal. To this end, applications in response to the NOFO are required to describe approaches, strategies, and methodologies that will promote the completion of enrollment; the retention of enrolled patients; the collection of biospecimens; and analyses of data that would better define factors that might improve long-term outcomes of patients with cirrhosis. Description of improving enrollment should discuss how to capture patients with cirrhosis who are also living with human immunodeficiency virus infection that reflects representation of the local and regional population of the participating center.
The scientific potential of the LCN data and biospecimen collection is expected to strengthen as each LCN study nears and achieves enrollment completion. The completed enrollment of the LCN Cohort study and LCN RESCU trial will provide an extensive database of serial clinical, biochemical, and radiologic results that can be used to shed light on the causes of disease progression ore regression. As such, each applicant to this NOFO must propose a single, separate Scientific Exploratory Specific Aim that must utilize and leverage the LCN data and biospecimen collection. The scientific pursuits should be distinct and non-overlapping with the scientific objectives of the LCN Cohort and RESCU Studies. Examples of topics; discovering, evaluating or determining biomarker assays of alcohol exposure or for development of hepatocellular carcinoma, portal hypertension, frailty and sarcopenia; analyses of genomic, proteomic, and other omic platforms; integration of bioinformatics or imaging processing and reading centralization in service of LCN research activities; analysis of environmental, dietary, or nutritional factors that might worsen compensated cirrhosis. This list of topics serves only as examples and is not complete. The intent of the Scientific Exploratory Specific Aim is to assess each applicant’s understanding of the LCN data and biospecimen resources and of pressing scientific issues pertaining to cirrhosis. Please note that the Scientific Exploratory Specific Aim will not be initiated or operationalized within the LCN unless future funds beyond this NOFO become available to specifically support these Exploratory Aims. For that reason, a budget for the Scientific Exploratory Specific Aim must not be included in the application to this NOFO.
Organization, Components, and Governance:
The Liver Cirrhosis Network will be administered under a Cooperative Agreement and be composed of Clinical Centers (CC), a single Scientific Data Coordination Center (SDCC), and the NIDDK and other components of the NIH as deemed appropriate by the NIDDK. The Liver Cirrhosis Network will be governed by a Steering Committee composed of investigators from each of the Clinical Centers, the Scientific Data Coordination Center, and the NIDDK and other components of the NIH as deemed appropriate by the NIDDK. Other subcommittees, working groups, and task forces of the Steering Committee previously established by the LCN will be renewed, prioritized and operationalized as necessary, such as committees on publications, ancillary studies, protocols, pathology, biospecimen use, and radiology. An Executive Committee comprised of at a minimum the Network Chair and Vice-Chair who will be determined by the Steering Committee with NIDDK concurrence at the re-establishment of the Liver Cirrhosis Network; the Program Director/Principal Investigator of the SDCC; and the NIDDK Project Scientist and Program Official; and other NIDDK personnel and other components of the NIH as deemed necessary by the NIDDK will be established to effect management decisions required between Steering Committee meetings, that is needed for efficient progress of the Network scientific activities. An independent Data and Safety Monitoring Board (DSMB) has been established by the NIDDK and will be continued to review protocols and monitor patient safety and performance of each Network 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 SDCC. All protocols or changes to protocols will require to be approved by a central or single Institutional Review Board, the Steering Committee, the Liver Cirrhosis Network Data and Safety Monitoring Board, and the NIDDK before initiation. Any specific collaboration involving the resources of the Liver Cirrhosis Network will require approval by the Steering Committee and the NIDDK Program Officer. Voting privileges for Steering Committee decisions will be by the Principal Investigator or designee of the award recipients for the Clinical Centers, the Scientific Data Coordination Center, and the NIDDK and other components of the NIH as deemed appropriate by the NIDDK. All face-to-face Steering Committee, DSMB, and other necessary face to face meetings requiring the presence of NIDDK and NIH personnel will be held in the Washington, DC/Baltimore metropolitan area or other suitable venue as appropriate for the operational efficiency of Network scientific activities and for the Programmatic oversight of cost-efficient Network resource management.
Clinical Centers will be responsible for operationalizing the LCN Cohort and LCN RESCU Studies. Additionally, Clinical Centers will be responsible for developing new protocol concepts conditional upon availability of Network resources, participating in their overall development, conducting the research, and disseminating research findings. For each investigational or therapeutic protocol, one CC will take the lead responsibility in conjunction with a protocol development subcommittee for drafting the protocol, although the Steering Committee will provide input and will be responsible for assuring development of a common protocol to be implemented by all of the Liver Cirrhosis Network CCs. The CC PD/PI leading the development of the protocol will also provide protocol oversight and management if implemented as a Liver Cirrhosis Network study. All CC PDs/PIs will be strongly encouraged to fully commit their center resources and efforts to the Network protocols. With the advent of electronic medical record (EMR) systems, it is desirable that CCs will be able to efficiently utilize their EMR for efficient screening of patient candidates for participation in the Liver Cirrhosis Network.
All individual CCs will be required to participate in a cooperative and interactive manner with one another, with the SDCC, and with the NIDDK and other components of the NIH in all aspects of the Liver Cirrhosis Network (see Terms and Conditions of Award). Only investigators who wish to carry out the protocols of the Liver Cirrhosis Network and agree to be governed by the policies and procedures of the Liver Cirrhosis Network and its Steering Committee should apply under this NOFO.
The SDCC in support of the Liver Cirrhosis Network research and data management activities will seek renewal through a separate NOFO, the details of which may be accessed at RFA-DK-26-309. In brief, the SDCC will support oversight and management of current ongoing LCN Cohort and LCN RESCU Studies, If new Steering Committee and NIDDK sanctioned protocol development is considered, the SDCC will provide sample size calculations, statistical advice, questionnaires, and data analysis; coordinate implementation, training, and logistical and management support for the conduct of the studies; support manuscript preparation; organize committee meetings; assist in the establishment, coordination, and management of a central or single Institutional Review Board for the Liver Cirrhosis Network; and provide overall study coordination and quality assurance, including coordination of the logistical activities of the Data and Safety Monitoring Board, the Steering Committee and other standing committees; coordination of the biospecimens, tracking, distribution, and eventual depositing of both data and biospecimens into the NIDDK Data and Biospecimen Repository as per NIDDK policy (https://repository.niddk.nih.gov/home).
The NIDDK/NIH will be responsible for organizing and providing support for the Liver Cirrhosis Network and will be involved substantially with the grant recipients as a "partner," consistent with the Cooperative Agreement mechanism. A designated NIDDK Project Scientist, who will provide scientific oversight, will monitor subject recruitment and study progress, ensure disclosure of conflicts of interest and Network adherence to NIDDK policies. The NIDDK will appoint 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.
Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A financial assistance 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 NOFO.
The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.
Required: Only accepting applications that propose clinical trial(s).
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) intends to commit $3,300,000 in FY 2026 to fund up to ten awards.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the 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 NOFO.
Higher Education Institutions - Includes all types
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
This is a Limited Competition funding opportunity intended to fund organizations who are grant recipients of RFA-DK-20-003.
Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 not allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.
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.
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 How to Apply-Application Guide.
This is a Limited Competition funding opportunity intended to fund Program Director/Principal Investigator who are grant recipients of RFA-DK-20-003.
This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.
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:
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.
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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.
All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.
All instructions in the How to Apply - Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
All instructions in the How to Apply - Application Guide must be followed.
All instructions in the How to Apply - Application Guide must be followed.
All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:
In the Research Strategy section, applications in response to this Notice of Funding Opportunity are required to address enhancing patient recruitment and retention to complete the enrollment goals of the LCN Cohort Study and the LCN RESCU Trial. Applications should describe approaches, strategies, and methodologies that will encourage and promote the completion of enrollment; approaches, strategies, and methodologies that will encourage and promote retention of enrolled patients in the two studies; and approaches, strategies, and methodologies that will encourage and promote the collection of biospecimens from participants enrolled in the LCN Cohort Study and the LCN RESCU Trial. The approaches to improving enrollment should discuss how to capture patients with cirrhosis who are also living with human immunodeficiency virus infection that reflects representation of the local and regional population of the participating center.
Applications in response to this NOFO are also required to include a separate Scientific Exploratory Specific Aim that must utilize and leverage the LCN data and or the biospecimen collection. The scientific pursuits should be distinct and non-overlapping with the scientific objectives of the LCN Cohort and RESCU Studies. The intent of the Scientific Exploratory Specific Aim is to assess each applicant’s understanding of the LCN data and biospecimen resources and of pressing scientific issues pertaining to cirrhosis. Please note that the Scientific Exploratory Specific Aim will not be initiated or operationalized within the LCN unless future funds beyond this NOFO become available to specifically support these Exploratory Aims. As such, a budget for the Scientific Exploratory Specific Aim must not be included in the application to this NOFO.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.
Other Plan(s):
All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:
Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply - 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 How to Apply- Application Guide must be followed.
All instructions in the How to Apply- Application Guide must be followed.
See Part 2. 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
Part I. 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 How to Apply-Application Guide.
This initiative is not subject to intergovernmental review.
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 Section 7.9.1 Selected Items of Cost.
Applications must be submitted electronically following the instructions described in the How to Apply 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 How to Apply 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.
Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.
Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.
Applicants are required to follow the instructions for post-submission materials, as described in the policy
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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.
Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score.
Significance
Innovation
Approach
Rigor:
Feasibility:
Investigator(s)
Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.
Environment
Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.
As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, 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, 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.
When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals 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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
As applicable, evaluate the full application as now presented.
As applicable, evaluate the progress made in the last funding period.
As applicable, evaluate the appropriateness of the proposed expansion of the scope of the project.
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.
For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by CSR, in accordance with NIH peer review policies and practices, 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.
Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.
Following initial peer review, recommended applications will receive a second level of review by the NIDDK Advisory Council or Board. The following will be considered in making funding decisions:
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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.
Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 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.
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.
A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.
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.
Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk. For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.
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: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:
All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.
By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.
Applicants and recipients are strongly encouraged to refer to the NIH Director’s Statement of Priorities, entitled “Advancing NIH’s Mission Through a Unified Strategy.”
Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).
Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.
Successful recipients under this NOFO agree that:
When recipients, subrecipients, or third-party entities have:
Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information.
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 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The Program Director(s)/Principal Investigator(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 clinical 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 policies and network/consortium 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 network/consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the network/consortium studies between grant recipient 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/consortium policies. Further, at the request of the NIDDK Program staff, any other network/consortium-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/consortium activities that includes access to any network/consortium generated resources (i.e., data and bio-samples), or study results that are not publicly available, or using the name of the network/consortium 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 or network/consortium. 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 (https://grants.nih.gov/policy/sharing.htm, and https://grants.nih.gov/faqs#/data-management-and-sharing-policy.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 Data Management and 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/Project Coordinator 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.
The NIDDK Program Official identified in the Notice of Award will:
Areas of Joint Responsibility include:
In addition to the interactions defined above, NIDDK Project Scientist or Project Coordinator 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 or Project Coordinator. The final structure of the Steering Committee and voting procedures will be established at the first meeting. The NIDDK Project Scientist or Project Coordinator will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NIDDK Project Scientist’s vote will represent NIH, as all NIH staff members will share one vote in support of the project. 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 Steering Committee.
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 or Project Coordinator may not serve as Chairperson. The NIDDK Program Official will review the Committee’s selection for potential bias, conflicts of interest, or lack of required expertise. If the Program Official has concerns regarding selection of the Chairperson which are not satisfactorily resolved, the Program Official may withhold concurrence if approved by the Director, Division of Extramural Activities, NIDDK based on written justification. In cases where Program Official concurrence is withheld, the Steering Committee will be required to make another selection.
External Consultants
An independent panel of External Consultants may be established by the Steering Committee. The External Consultants may periodically review interim progress of the project(s) and provide reports to the Steering Committee. Members of the panel of External Consultants 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. The NIDDK Program Official will review the Committee’s selections for potential bias, conflicts of interest, or lack of required expertise. If the NIDDK Program Official has concerns regarding selection of one or more External Consultants which are not satisfactorily resolved, the NIDDK Program Official may withhold concurrence if approved by the Director of NIDDK Division of Extramural Activities based on written justification. In cases where NIDDK Program Official concurrence is withheld, the Steering Committee will be required to make another selection.
Dispute Resolution
Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIH may be brought to dispute resolution. A dispute resolution panel will be composed of three members --one selected by the recipient (or the Steering Committee, with the NIDDK member not voting), a second member selected by NIH, and the third member with relevant expertise elected by the two prior selected members. These special dispute resolution procedures in no way affect the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16.
Consistent with the 2023 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.
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 Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.
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 Section 8.6 Closeout. 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 2 CFR Part 200.301.
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.
Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Email: NIDDK_DDN@nih.gov
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Grants Management Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Email: NIDDKGMBManagementTeam@niddk.nih.gov
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 2 CFR Part 200.