Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

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

Funding Opportunity Title
Mass Spectrometric Assays for the Reliable and Reproducible Detection of Proteins/Peptides of Importance in Type 1 Diabetes (T1D) Research (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of RFA-DK-17-019
Related Notices

None

Funding Opportunity Announcement (FOA) Number
RFA-DK-21-031
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.847
Funding Opportunity Purpose

 

This Funding Opportunity Announcement (FOA) encourages applications from institutions/organizations proposing the development and/or validation of targeted mass spectrometric assays (e.g. Multiple Reaction Monitoring) for proteins and peptides of primary interest to the type 1 diabetes research community [e.g. glucagon and other pro-glucagon derived peptides, C-peptide, insulin, pro-insulin, Glycated CD59, Islet Amyloid Polypeptide (IAPP), Chromogranin A (CgA), and chromogranin B (CgB)]. The proposed assays should be highly reproducible, easily transferable to other laboratories, and validated in human plasma or serum. This might also require the development of appropriate community standards, and reference materials when not already available.

 

Key Dates

Posted Date
July 14, 2022
Open Date (Earliest Submission Date)
September 26, 2022
Letter of Intent Due Date(s)

September 26, 2022

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 26, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

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.

Expiration Date
October 27, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

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

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

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

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

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


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Many assays in basic and clinical science research rely exclusively on antibodies. However, there are no widely accepted guidelines or standardized methods to determine the validity of these reagents. Furthermore, many recent publications have highlighted the limitations of commercial antibodies including failure to detect the intended target. The rigor and reproducibility of many assays commonly used by researchers in the field of type 1 diabetes could be substantially improved applying Mass Spectrometry (MS) instead of relying only on antibodies.

For some analytes, mass spectrometric assays that are more specific and less variable than previous measurements have been already developed. For example, for insulin and c-peptide the feasibility of using Liquid Chromatography-Mass Spectrometry (LC-MS) in a high-throughput clinical laboratory was demonstrated. However, these methods might need further validation. For glucagon and other proglucagon derived peptides, a highly reproducible assay that combines the use of a monoclonal antibody for enrichment and mass spectrometry for the detection and quantitation was developed. However, the monoclonal antibody used in the enrichment step was developed in house and is not easily available to the scientific community. More recently, a mass spectrometers manufacturer used a combination of solid-phase extraction (SPE) and µElution to develop an assay for glucagon in human plasma. Although this assay might need further validation, it demonstrated that it is possible to reach a Limit of Detection in the low pg/mL with very simple and inexpensive fractionation steps prior to a targeted mass spectrometry experiment like a Multiple Reaction Monitoring (MRM) experiment. Novel interfaces, that can be placed in the front-end of the mass spectrometer, can also be used for reducing chemical noise and matrix interference, leading to targeted MS assays that are more robust. Furthermore, these types of assays with simple pre-fractionation steps are in many cases easy to multiplex.

Purpose and Research Objectives

This FOA is inviting applications proposing the development of targeted mass spectrometric assays for proteins and peptides of primary interest in type 1 diabetes research [e.g. . glucagon and other pro-glucagon derived peptides, C-peptide, insulin, pro-insulin, Glycated CD59, Islet Amyloid Polypeptide (IAPP), Chromogranin A (CgA), and chromogranin B (CgB)]. These assays should be validated quantifying the endogenous proteins and peptides of interest in human plasma/serum and should use labeled internal standards. These assays should be qualified demonstrating accurate quantification, precision, specificity, analytical sensitivity, Limit Of Detection (LOD), and Lower Limit Of Quantification (LLOQ) (see CPTAC guidelines). Ideally, these assays would have a small number of enrichment/fractionation steps prior to the MS analysis and would not use an antibody for enriching the analyte of interest. However, when well justified monoclonal antibodies can be used as an enrichment step for developing Immuno-MRM assays or other similar assays. The goal should be to develop assays that are easily transferable to any laboratory that has appropriate expertise and access to a mass spectrometry facility. For this purpose, the use of easily accessible and inexpensive separation steps such as SPE and µElution are encouraged. The proposed assays should be highly reproducible and transferrable and this might also require the development of appropriate community standards, and reference materials when not already available.

Although a multiplexed assay that includes all analytes of interest would be highly desirable, it may not be feasible. In this case individual assays or assays for subgroups of specific analytes would be also of interest. For example, a multiplexed assay for Glucagon, Pro-Insulin, Insulin, and c-peptide would be highly desirable. Even a multiplexed assay for only Insulin and Glucagon, if feasible, would be desirable. A plan for multiplexing as many assays as possible or for developing several multiplexed assays for subgroups of analytes of special interest should be included.

It should be emphasized that the analytes listed in this FOA are only examples of analytes of potential interest and it is up to the applicant(s) to make a case for what are the analytes of main interest to the type 1 diabetes research community. The applicant(s) should provide a compelling rationale for validating or developing novel mass spectrometric assay for each specific analyte or group of analytes. The applicant(s) might propose the development and/or validation of a larger or smaller number of the analytes listed in this FOA. The most important objective to achieve is that the mass spectrometric assays proposed to be validated and/or developed are of primary interest to the type 1 diabetes research community and that the proposed project is feasible within the allowed budget for this FOA.

The NIDDK will work together with the awardees in facilitating the identification and prioritization of the proteins and peptides of interest in type 1 diabetes. However, the applicants are strongly encouraged to include in their application a list of proteins/peptides that are present in human plasma/serum and that are of potential interest to the type 1 diabetes research community. A plan for assay prioritization and for assessing the interest in the type 1 diabetes research community during the progression of the project must be included.

The NIDDK envisions that a successful application is likely to require an interdisciplinary team that includes expertise in clinical chemistry, diabetes, and targeted mass spectrometry assay development.

Cooperative relationships and data sharing

The awardees are expected to work closely and collaboratively with the NIDDK in achieving the goals stated in the FOA.

A plan for sharing and disseminating the successfully developed assays to the scientific community is required. This plan should include the deposition in a public portal, such as the CPTAC, of the assays characterization/validation data, the metadata, and of the Standard Operating Procedures (SOPs) to perform the assays.

The NIDDK will appoint a NIDDK Project Scientist. An External Scientific Panel (ESP), consisting of two to four independent expert scientists will be selected and appointed by the Principal Investigator(s) after consulting with the NIDDK Project Scientist. All Principal Investigators must participate in a bimonthly teleconference with the NIDDK assigned Project Scientist. The ESP and Project Scientist will participate in an annual site visit. Awardees are required to participate in this site visit as well, as to budget for the travel and participation of the ESP.

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

Section II. Award Information

Funding Instrument

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

Application Types Allowed
New

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

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

The NIDDK intends to commit up to $1.0 million to fund one award in Fiscal Year 2023.

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to $700,000 direct costs per year, exclusive of indirect costs on subcontracts, per year. Budgets are expected to reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 4 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Required Registrations

Applicant Organizations

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

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

 

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

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

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

The letter of intent should be sent to:

John F. Connaughton, Ph.D.
Chief, Scientific Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7797
Email: NIDDKLetterofIntent@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy:

The applicant(s) should explain the reasons for validating or developing a novel mass spectrometric assay for each specific analyte or group of analytes.

The applicant(s) should describe how the type 1 diabetes research community could benefit from the availability of the standardized and validated assays.

The applicant(s) should describe a plan for assay prioritization and for assessing the interest in the type 1 diabetes research community during the progression of the project.

An assays qualification plan consistent with recent CPTAC guidelines should be included. This plan should include demonstration of accurate quantification, precision, specificity, analytical sensitivity including Limit Of Detection (LOD), Upper Limit Of Quantification (ULOQ), and Lower Limit Of Quantification (LLOQ). This plan should also include the validation for quantifying the endogenous peptides and proteins of interest in human plasma or serum.

A plan for multiplexing the assays or developing multiplexed assays for subsets of the peptides/proteins of interest should be included.

Applicants should describe how the proposed assays will be made easily available to the scientific community.

 

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:

It is the goal of NIDDK to further advance research by making resources, data, and reagents generated in whole or in part using funds from these U01 awards widely available to the research community with minimal restrictions.

A plan for sharing and disseminating the successfully developed assays to the scientific community is required. This plan should include the deposition in a public repository, such as the CPTAC. All applications, regardless of the amount of direct costs requested for any one year, should address how they will share unique reagents, the assays characterization and validation data (including validation for accuracy, quantification, precision, specificity, analytical sensitivity, Limit Of Detection (LOD), Upper Limit Of Quantification (ULOQ), and Lower Limit Of Quantification (LLOQ), and Standard Operating Procedures (SOPs) necessary for replicating the assays.

All applicants are also encouraged to work with the NIDDK Information Network (dkNET), for the proposed resource be catalogued, indexed and tracked, and made easily findable by the NIDDK research community.

Appendix:

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 FOA for information on registration requirements.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NIDDK, 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://www.nlm.nih.gov/cde/index.html) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

Overall Impact

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

Scored Review Criteria

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

 

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?

Specific to this FOA:

How appropriate is the explanation for validating and/or developing a novel mass spectrometric assay for each specific analyte or group of analytes that is proposed?

How adequate is the plan for assay prioritization and for assessing interest in the type 1 diabetes research community during the progression of the project?

How appropriate is the plan for qualifying the assays?

How appropriate is the plan for making the validated assays easily available to the scientific community?

 

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?

Additional Review Criteria

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

   

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.

 

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.

 

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.

 

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.

 

Not Applicable.

 

Not Applicable.

 

Not Applicable.

Additional Review Considerations

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

 

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

 

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).

 

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).

 

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.

 

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group 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 be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council (NDDKAC). The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS 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 (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this 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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement U01, 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 working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Awardee(s) will be primarily responsible for defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.

The Principal Investigator/Program Director will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations, and policies.

The Awardee will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH policies.

All staff of the Awardee will maintain the confidentiality of the information developed by the investigations, including, without limitation, study protocols, data analysis, conclusions, as well as any confidential information received by third party collaborators.

Awardees must analyze, publish and/or publicly release and disseminate results, data, and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the FOA.

All staff of the Awardee will be required to participate in a cooperative and interactive manner with NIH staff.

Awardees are expected to share data, materials, methods, and SOPs of the developed mass spectrometric assays with the scientific community.

Awardees will submit a list of milestones and project deliverables to the NIDDK.

• Awardees agree that third party collaborations (including both industry and academia) should be governed by a research collaboration agreement (e.g. CTA, RCA, etc.) with terms that ensure that the developed assays, the validation data, and SOPs will be made available to the scientific community through a public portal in accordance with the Cooperative Agreement and all applicable NIH policies and procedures. The NIDDK Program staff will consult with others at NIH including the Technology Advancement Office.

Awardees agree that all hybridomas and recombinant antibodies clones developed within this cooperative agreement or used in the assays will be made available through the Developmental Studies Hybridoma Bank (http://dshb.biology.uiowa.edu/).

Awardees must operate in accordance with processes and goals as delineated in the Funding Opportunity Announcement.

Upon completion or termination of the research project(s), the awardees are responsible for making all developed assays, the validation data, and SOPs broadly available and making them accessible to the research community according to the NIH-approved data sharing and dissemination plan. This should be accomplished on timely manner and no later than the end of the study.

The awardee will be responsible for accepting and implementing the goals, priorities, procedures, protocols, and policies agreed with the ESP and the NIDDK.

Awardees agree to organize a yearly site visit based on the availability of the ESP members and of the NIDDK Project Scientist, and to reimburse the ESP members for the travel expenses for attending this site visit following the NIH travel guidelines.

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 stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.

An NIDDK Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIDDK Program Official as follows:

  • The NIH Project Scientist will coordinate and facilitate the research projects, participate in the bi-monthly call, and attend the annual site visits.
  • The NIH Project Scientist and Program Officer will review the scientific progress, cooperation in carrying out research, and maintenance of high-quality research, and review the project for compliance with the stated goals and objective of this FOA. Based on this review, the Project Scientist in conjunction with the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of scientific progress or adherence to the objectives and goals of this FOA. Review of progress may include regular communications between the Principal Investigator/Program Director and NIH staff, additional site visits for discussions with awardee research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic review of progress.

The NIDDK reserves the right to terminate or curtail any study or any individual award in the event of (1) substantial shortfall in data collection or submission, quality control, or other major breach, (2) substantive changes in a study protocol that are not in keeping with the objectives of the FOA, or (3) concerns related to human subject safety that prompt the need for premature termination.

The NIH may enlist additional scientific consultants as necessary from within the NIH whose function will be to assist the Project Scientist in carrying out the goals and aims of the approved studies.

The NIH Project Scientist will have substantial scientific programmatic involvement in research coordination and performance monitoring. The dominant role and primary responsibility for these activities resides with the awardee; however, specific tasks and activities in carrying out the studies will be shared among the awardees and the NIH Project Scientist.

The NIH Project Scientist serves as a resource with respect to facilitate interaction with other ongoing NIH activities.

The NIH Project Scientist or designee may coordinate activities among awardees by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data and in the publication of results.

The NIH Project Scientist may review procedures for assessing data quality and monitor study performance.

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

Areas of Joint Responsibility include:

After the award an initial face-to-face meeting between the Project Scientist, other relevant NIH staff, and the awardees will be scheduled. This meeting will have the main purpose of jumpstarting the project and evaluating and modifying as necessary the proposed milestones.

The Principal Investigator(s) and NIDDK Project Scientist will collaborate and invite scientific experts with relevant scientific expertise to provide feedback to the study group. These experts will constitute the Expert Scientific Panel (ESP).

Expert Scientific Panel (ESP)

The Principal Investigator(s) in consultation with the Project Scientist will establish a panel of two to four independent scientific experts (ESP). The NIDDK Project Scientist, ESP, and the Principal Investigator(s) will meet at least once a year. The ESP will be updated on progress and give feedback to the NIH and the Principal Investigator(s) on adjustments that might benefit the research projects.

The ESP might advise the Principal Investigators and the NIDDK staff of scientific developments and opportunities that may enhance the achievement of the study goals.

Dispute Resolution

Disagreements that may arise in scientific/technical matter or programmatic matters (within the scope of the award) between award recipients and the NIDDK may be brought to arbitration. The arbitration panel will be composed of the Principal Investigator, one NIH designee, and a third designee from the independent panel of review experts. This special dispute resolution procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.

3. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Scientific/Research Contact(s)

Xujing Wang, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-451-2862
Email: xujing.wang@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Todd Le
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phone: 301-594-7794
Email:
Todd.Le@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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

This FOA is supported under the authority of P.L. 116-94, Further Consolidated Appropriations Act, 2020; Section 402. Diabetes Programs.

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