Department of Health
and Human Services (HHS)
and Human Services (HHS)
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
U01 Research Project – Cooperative Agreements
None
This Funding Opportunity Announcement (FOA) invites applications for a Central Primary Reference Laboratory (CPRL) to provide support for the harmonization and standardization of laboratory measurements critical for clinical research in type 1 diabetes. The CPRL will provide administrative functions to coordinate harmonization efforts among clinical laboratories and commercial suppliers of reagents and methods, and will provide measurements of reference values for C-peptide and HbA1c measurements.
September 20, 2021
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| October 20, 2021 | October 20, 2021 | Not Applicable | March 2022 | May 2022 | July 2022 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
The primary objective of this cooperative agreement is to improve and standardize HbA1c measurements and data interpretation across clinical systems and national harmonization programs as well as to standardize C-peptide measurements. The reduction in risk of complications of diabetes with improved HbA1c as demonstrated in the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) underscores the need to measure HbA1c with sufficient reliability such that clinical laboratory results can be directly related to these studies and, therefore, to the risk for development or progression of diabetes-related chronic complications. Because clinical care providers are adjusting medical therapy based on HbA1c measurement and excessive or inadequate therapy can harm patients, it is imperative that the accuracy of this key test as performed for clinical care continues to improve. In the research sphere, the measurement of C-peptide used to monitor endogenous insulin production is the basis for identifying successful therapeutics to delay the progression of type 1 diabetes. There is increasing evidence, including data from the DCCT study, that preservation of even a low level of endogenous insulin production in people with type 1 diabetes is associated with significantly fewer diabetes complications over the longer term. Therefore, efficient, accurate, and precise measurement of C-peptide is important for current and future research with the goal to prevent type 1 diabetes in those at risk. This Funding Opportunity Announcement will provide support for a Central Primary Reference Laboratory (CPRL) to standardize and improve the measurement of HbA1c and C-peptide.
Background
Diabetes mellitus is a chronic disorder characterized by insulin deficiency, hyperglycemia, and high risk for development of complications of the eyes, kidneys, peripheral nerves, heart and blood vessels. The disease is highly prevalent, affecting over 29 million people in the U.S. The disease comes in two major well characterized forms, type 1 diabetes, characterized by autoimmune-mediated destruction of insulin producing pancreatic beta cells, and occurring mainly in children and young adults, and type 2 diabetes, characterized by insulin resistance and associated with obesity, primarily in adults. It is estimated that approximately 1 in every 7 health care dollars spent in the U.S. goes to diabetes care - mostly for treatment of the chronic complications which occur in both forms of the disease. In the U.S., diabetes is the most common cause of blindness in working age adults, kidney failure, and non-traumatic limb amputation.
The landmark nine-year Diabetes Control and Complications Trial (DCCT), completed in 1993, showed conclusively that the risk for development and progression of the chronic complications in patients with type 1 diabetes mellitus could be dramatically reduced with improved blood glucose control as assessed by serial glycohemoglobin [GHB or hemoglobin A1c (HbA1c)] determinations. HbA1c has been shown to be a reliable index of average blood glucose during the previous 2-3 months that is used routinely to monitor glycemic control in individuals with diabetes. Based on the DCCT results, the American Diabetes Association (ADA) and other professional groups have developed a series of specific diabetes treatment guidelines using HbA1c as a measure of mean blood glucose. However, lack of standardization of HbA1c assay methods among different laboratories prevented optimal use of the test in the clinical setting. Efforts to reduce complications of diabetes through improved glycemic control required standardization of clinical HbA1c assays so that tests done for medical care of people with diabetes would be comparable to the levels of HbA1c proven to reduce complications in the DCCT. Subsequent studies showed the feasibility of standardizing HbA1c assays, and a candidate reference method for HbA1c was proposed. Early efforts to standardize HbA1c values among clinical laboratories by using a "universal calibrator" proved feasible for some assay methods. Later studies showed, however, that such an approach, although relatively simple, did not work for some methods currently in use in the clinic. Thus, it was decided that the best way to proceed with the standardization of the assay across clinical labs to the DCCT reference values was to start at the manufacturing level, with the verification of method standardization using fresh sample comparisons with the Reference Method.
HbA1c measurement standardization has become even more important in recent years. There is increased use of the test, with rising rates of diabetes. The FDA has utilized improvements in HbA1c as an outcome measure for approval of new therapies for diabetes. In 2010, the ADA sanctioned the use of HbA1c as one option for diagnosis of diabetes and pre-diabetes. Thus, there is now a critical need for accuracy and precision near the normal range in addition to the clinical target range for diabetes treatment.
In an effort to standardize these methods and to reduce the variation among them, the American Association for Clinical Chemistry established the National Glycohemoglobin Standardization Program (NGSP). The NGSP evaluates, sets accuracy standards, and certifies methods for the measurement of HbA1c with the goal of standardizing the glycohemoglobin test. This initiative has resulted in a substantial improvement in the comparability, reliability, and precision of assay methods. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) work group on Standardization of HbA1c then developed a reference measurement procedure that has been approved by all IFCC member societies. The fact that HbA1c is now recommended for diagnosis of diabetes and prediabetes reinforces the requirement that HbA1c results be accurate. More specifically, constant monitoring of the analytical performance of the assay and quality control is needed to achieve the goals of intra-laboratory CV <2% and inter-laboratory CV <3.5%.
The DCCT established the importance of another key laboratory measurement in type 1 diabetes. C-peptide is a stable and detectable non-functional cleavage product of insulin found in serum. Measurement of C-peptide is used to monitor endogenous insulin production in people with diabetes who are receiving exogenous insulin as therapy. There is increasing evidence, including data from the DCCT study, that preservation of even a low level of endogenous insulin production in people with type 1 diabetes is associated with significantly fewer diabetes complications. DCCT participants with measurable C-peptide were able to achieve better glycemic control with less risk of hypoglycemia and had fewer long-term complications of diabetes. These data suggest that functional preservation of endogenous insulin production as assessed by C-peptide has clinical benefit. Typically, the new onset type 1 diabetes patient can expect to see their endogenous insulin production (as measured by mixed meal-stimulated C-peptide) decline over the first 1-2 years after diagnosis, as residual insulin producing beta cells are lost to autoimmune destruction. Therefore, recent trials of clinical interventions in new onset subjects are designed to delay progression of beta cell loss and preserve C-peptide production or to delay its decline over 1 to 2 years. Preservation of C-peptide production at 1 or 2 years as a clinical trial endpoint has been accepted by the FDA.
Measuring C-peptide levels with highly sensitive and standardized methods is therefore important now to accurately implement and interpret clinical trials to identify therapeutic interventions capable of reversing or delaying progression of the disease at onset. C-peptide measurements are also important for research that seeks to disrupt the disease process before symptoms appear. It has been recently demonstrated that the new therapeutic, teplizumab, first shown to preserve C-peptide in new onset clinical trials, also delays progression to symptoms when given at the prodromal Stage 2. Improving, harmonizing, and standardizing C-peptide measurements continue to be important as additional interventions and combination of agents are tested for clinical benefit.
To assist in C-peptide assay harmonization, an ADA endorsed C-peptide standardization committee was established and international C-peptide comparison studies were conducted. As a result of many years of comparison studies using pure C-peptide standards and patient samples, the committee concluded that patient samples work best to improve comparability and calibration among assays, and to reduce variability. More recently, a LC/MS reference method for C-peptide was developed and used to improve comparability of results. A second reference laboratory procedure is also underway to fulfill the requirements of manufacturer acceptability to list the reference method with the Joint Commission on Traceability in Laboratory Medicine. Newer studies seek to develop improved direct detection methods including LC/MS and make them applicable to research clinical laboratory settings.
Scope
a) The laboratory is responsible for establishing and maintaining the DCCT primary reference method that analyzes HbA1c by high performance liquid chromatography (HPLC) using Bio-Rex 70 resin.
b) The laboratory is responsible for establishing a network of reference laboratories, all of which maintain reference methods, or precise methods traceable to the reference method.
c) The laboratory is responsible for monitoring the Network Laboratories.
d) The laboratory is responsible for interacting with manufacturers of HbA1c methods, providing assistance in standardizing their methods and then providing comparison data for certification of traceability to the DCCT.
e) The laboratory is responsible for providing fresh whole-blood specimens, in the clinical range of 4-14% Hb1Ac, for use in comparison studies and monitoring laboratory performance for this project.
f) The laboratory is responsible for providing assessment of effectiveness of the program through evaluation of independent Proficiency Testing data from the College of American Pathologists (CAP).
g) The laboratory is responsible for providing data to validate and improve the use of HbA1c as an official diagnostic measure for diabetic disease.
h) The laboratory is responsible for maintaining a public website providing information on the quality of HbA1c assays and methods as well as information on the suitability of assays and methods for particular populations (e.g. hemoglobin variants).
i) The laboratory will foster continuous improvement in the accuracy and reliability of clinical HbA1c assays in use in the U.S., including analyses of inferences based on rare variants and other factors.
j) The laboratory will convene regular meetings to foster harmonization efforts in the U.S. with international efforts to improve and standardize HbA1c measurement.
k) The laboratory is responsible for establishing and maintaining a C-peptide standardization program for select laboratories, particularly those serving major NIH supported clinical research projects.
l) The laboratory is responsible for coordinating the establishment and maintenance of two reference method laboratories for C-peptide and conducting the manufacturer re-calibration studies, including preparing and evaluating primary and secondary reference materials, and internal standards.
m) The laboratory will work with CAP to establish accuracy-based surveys using unprocessed serum.
n) The laboratory is responsible for external Quality Control (QC) and/or Proficiency Testing (PT).
o) The laboratory is responsible for receiving, managing, and analyzing data obtained from the primary and secondary reference laboratories for HbA1c and C-peptide.
p) The laboratory is responsible for developing and maintaining a public website providing information on the quality of C-peptide assays and methods as well as information on the suitability of assays and methods for particular populations (e.g. at risk groups, or people with long-standing T1D).
q) The laboratory PD/PI will be a member of the CPRL Steering Committee (SC). The SC is the main governing body of the network, and works with the NIDDK to oversee the implementation of the program. The laboratory will be working closely with all the other laboratories involved in a collaborative and interactive manner.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NIDDK intends to commit $550,000 in FY 2022 to fund one award for 5 years.
The requested budget may vary across years and may not exceed $350,000 per year in direct cost, exclusive of subcontract F&A. Budgets are expected to reflect the actual needs of the proposed project.
The project period must not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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 Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:
John F. Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
Telephone: 301-594-7797
Email: NIDDKLetterofIntent@mail.nih.gov
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 FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
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.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
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.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (https://cde.nlm.nih.gov/home/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their project
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
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.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
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.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable.
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
Not Applicable.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NIDDK Advisory Council. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
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.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
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. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIDDK will designate program staff, including a Program Officer and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.
The NIDDK will consult External Experts with relevant scientific expertise to review the progress of the research projects and to advise NIH staff of scientific developments and opportunities that may enhance the achievement of the study goals.
An NIH IC Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:
Areas of Joint Responsibility include:
Through the Awardee, Steering Committee and NIH staff, the study members will cooperatively develop and implement processes to submit information and data, determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the Funding Opportunity Announcement.
Steering Committee
This SC will operate to develop collaborative protocols, identify impediments to success and strategies to overcome them, develop shared tools for disseminating information about the projects, and identify opportunities for sharing techniques, materials, information and tools.
External Experts
Dispute Resolution
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Salvatore Sechi, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8814
Email: sechi@nih.gov
Najma Begum, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8894
Email:begumn@mail.nih.gov
Craig E. Bagdon
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-2115
Email: Craig.Bagdon@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 45 CFR Part 75.
This FOA is supported under the authority of P.L. 116-260, Consolidated Appropriations Act, 2021; Section 302. Diabetes Programs.
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