Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute on Aging (NIA)
National Institute of Environmental Health Sciences (NIEHS)

Funding Opportunity Title

Telomeres as Sentinels of Environmental Exposures, Psychosocial Stress, and Disease Susceptibility: A Methods Comparison Study (U01 Clinical Trial Optional)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-AG-19-023

Companion Funding Opportunity

RFA-AG-19-022, U24 Resource-Related Research Projects – Cooperative Agreements

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

93.866, 93.113  

Funding Opportunity Purpose

This U01 Cooperative Agreement Funding Opportunity Announcement (FOA) will support  Methods Comparison Projects to serve three main functions: (1) to conduct a joint effort among telomere researchers to determine the relationship between different telomere length (TL) methods, inter-assay variability, and the factors that influence results; (2) to contribute to development of best practice recommendations for assay protocols for TL measurement for different types of studies, with a focus on population-based health research, including biological sample collection, storage, and processing; laboratory methods; data analysis; and reporting requirements; and (3) to repurpose existing methods or develop new methods to enhance the use of TL measurement.

The U01 Methods Comparison Projects will be expected to conduct cross-validation involving other labs (3-4) supported under this cooperative agreement to develop a set of recommendations for assay protocols for telomere measurement for different types of studies and develop best practice guidelines for population-based TL research. This will be done in coordination with the U24 Telomere Research Network/Collaboratory award made in response to FOA (RFA-AG-19-022). Please refer to the NIA website regularly for updates, frequently asked questions (FAQs), and other announcements related to this FOA and the companion FOA.         

Key Dates
Posted Date

August 15, 2018

Open Date (Earliest Submission Date)

November 3, 2018

Letter of Intent Due Date(s)

November 3, 2018

Application Due Date(s)

December 3, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May 2019

Advisory Council Review

August 2019

Earliest Start Date

September 2019

Expiration Date

December 4, 2018

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the 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 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    This U01 Cooperative Agreement Funding Opportunity Announcement (FOA) will support 3-4 independent Methods Comparison projects to further develop/augment and evaluate current methods to assess telomere function, focusing on telomere length (TL), for population-based research. These projects will support three main activities: (1) to conduct a collaborative Methods Comparison Study to determine the relationship between different TL assays, inter-assay variability, and the factors that influence results; (2) to contribute to the development of best practice recommendations for assay protocols for TL measurement for different types of studies, with a focus on population-based health research, including recommendations for biological sample collection, storage, and processing; laboratory methods; data analysis; and reporting requirements; (3) to repurpose existing methods or develop new methods to enhance the use of TL measurement.

    The U01 Methods Comparison Projects will be expected to conduct the TL measurement methods comparison study involving other labs (3-4) supported under this cooperative agreement. Results from the methods comparison study will support the development of recommendations for assay protocols for telomere length (TL) measurement and of guidelines for telomere length research in population-based studies, in a transparent manner through collaboration with the telomere research community. This will be done in coordination with the U24 Telomere Research Network/Collaboratory award made in response to FOA (RFA-AG-19-022). The goal is to cross-validate TL measurements from reference samples and establish best practices and optimized methods for future studies. Moreover, attention will be given to increased efficiency/proficiency of these methods for better throughput and cost effectiveness.  

    Please refer to the NIA website regularly for updates, frequently asked questions (FAQs), and other announcements related to this FOA and the companion FOA.

    Background

    A growing number of investigators across a range of scientific fields have become intrigued by the role of telomeres in health and aging, with respect to both their functional properties and predictive value. In addition to the direct role of telomere dysfunction in certain diseases, telomeres also appear to be “sentinels” for environmental exposures and psychosocial stress, potentially representing a readout of the accumulated life history of exposures of an individual. However, inconsistencies in epidemiological findings, concerns about comparability of telomere assessments across multiple studies, together with emerging findings that early life exposures may play an important role in setting TL, and other exogenous insults that perturb TL, suggest that more research is needed to understand effects of environmental exposures and life stressors on telomere function and health outcomes.

    A recent NIEHS/NIA workshop brought together experts from basic telomere biology, medicine, biopsychology, epidemiology, and related fields to explore and discuss the potential use and value of TL as a biomarker for environmental exposures, psychosocial stress, and disease susceptibility in population-based research. A workshop summary is available here: https://www.nia.nih.gov/research/dbsr/telomeres-sentinels-environmental-exposures-psychosocial-stress-and-disease. Experts discussed how insights from basic biological science can advance epidemiological and clinical investigations, and vice versa. Discussions also addressed additional factors that need to be measured alongside telomeres (e.g., telomerase expression/activity), interactions between genes and the environment (including both the physical and the social environment) on health, tissue-specific effects, and the potential to use surrogate tissues in situations where the “target” tissue (e.g., the brain) is inaccessible. Building on this productive dialogue, attendees highlighted an immediate need to determine the comparability of results obtained using different assays and across different cell types; to set standards for sample preparation, DNA extraction, and reporting of assay protocols; and to make recommendations for conducting telomere assessments in different research contexts (e.g., lab-based vs. population-based). Continued dialogue across research disciplines will be essential to move this agenda forward. The participants reached consensus concerning the need for definitive studies on the methods and universal standards for laboratory protocols. This will involve multiple labs working together along with the appropriate biostatistics expertise. Participants also recommended that separate sets of recommendations be developed for laboratory, clinical, and population-based studies given that no single approach would meet the needs of all types of studies.

    NIA and NIEHS extramural and intramural programs have longstanding and growing investments in exposure science assessing the impact of environmental exposures and psychosocial stress on premature aging and disease susceptibility, so establishing standards for the measurement of TL and other biomarkers is crucial. Resolving measurement issues for the field and communicating best practice guidelines for reporting on assay protocols in publications and grant applications will strengthen the foundations of this science. The network will both support this need and enable continued transdisciplinary dialogue among telomere scientists across multiple disciplines who, until the recent meeting, had not gathered in one place to discuss shared concerns and priorities for the field. 

    Scope

    This FOA invites applications for Methods Comparison Projects that will address recommendations from the recent workshop through three sets of activities:

    (1) To conduct a collaborative methods comparison study developed by the Telomere Research Network (TRN) for TL measurement in coordination with the U24 awarded under FOA (RFA-AG-19-022), to develop guidelines for telomere length research feasible for clinical or population-based research;

    (2) To contribute to the development of a set of recommendations for TL measurement protocols; and

    (3) To repurpose existing methods or develop new methods to enhance the use of TL measurement. 

    To effectively accomplish these activities, the leadership of the U01 should have expertise in basic telomere biology, telomere length measurement, population health, and biostatistics.

    Required Activity 1: Conduct a collaborative methods comparison study

    The first activity—to be completed in the first two years of the grant—will conduct a TL measurement comparison study in a transparent manner through collaboration with the other U01s funded through this FOA and input from the broader telomere research community, with the aim of informing guidelines for measuring telomere length that are appropriate for population-based studies. As different methods are likely to be appropriate in different settings and no single method is likely to meet the needs of all the types of studies, multiple approaches are being invited. Common criteria include the following: these studies should differentiate between actively growing versus frozen or archived cells and be applicable to methods suitable for population-based studies (e.g., qPCR). Common parameters for this collaborative work, including the TL methods comparison studies, will be established by a Steering Committee including all U01 PIs, coordinated by the U24 Telomere Research Network (TRN; RFA-AG-19-022), at a kick-off meeting in the fall of 2019. The intended goals are to determine the relationship between TL measurement assays used in population health (e.g., q-PCR) and the gold standard telomere length assays (e.g., TRF and flow-FISH), impacts of cell heterogeneity on measured TL, inter-assay variability, and the factors that influence results (e.g., DNA extraction, storage, batch effects), in order to develop recommendations for TL research around biological sample collection, storage, and processing; laboratory methods; data and statistical analysis; and reporting requirements for population-based studies. Each U01 will conduct its own analyses, and routinely share protocols and data with the consortium, facilitated by the TRN. This effort will build upon previous efforts to improve TL measurements with the opportunity to test optimal parameters (e.g., DNA extraction and sample storage conditions) and apply new knowledge to refine existing or develop new telomere length measurement techniques in a collaborative environment that strongly draws from the recommendations made by NIEHS/NIA workshop participants. These studies will be iterative, involving comparative assessments between methods and within method tests and retests for reproducibility. NIH intramural labs will produce and provide standard reference samples (whole cells that need to be processed) to be tested across the labs.

    To capture a range of TL, cells will be provided to individual labs to perform duplicate runs to complete the methods study to optimize current protocols and assay conditions for the TL measurement to meet the goals of Activities 1 and 2. Human cells (Peripheral Blood Mononuclear Cells (PBMCs) from cord blood, young and older individuals (to properly account for the dynamic range in TL) will be provided by intramural NIA. These cells will be shipped on dry ice and provided to the U01 labs in a random and blinded fashion (barcoded). For Activity 3, U01 labs are expected to provide their own cells when developing and or refining new assays to measure TL. The U01 labs will continuously deposit the TL measurement data, along with the parameters necessary to conduct the assay including biological sample collection, storage, and processing; laboratory methods; data and statistical analysis; and reporting requirements into a repository decided by the Steering Committee (see below).

    In fulfilling these activities, individual labs are expected to submit detailed specific aims on how they would conduct an optimal methods comparison study that includes approaches appropriate for population-based studies (e.g., qPCR) that could inform standards for the field. Details for TL assessment in actively growing versus frozen or archived cells (selecting cells commonly used for TL measurement in population-based studies; e.g., stored whole blood and buffy coat, buccal cells, saliva, and dried blood spots) should include: sample collection; cell preparation; DNA extraction method and sample storage conditions; assay parameters, including reagents; analysis methods, including statistical approaches; selection of reference standard and controls; issues related to batch analyses; standardization and automation considerations; and reporting requirements. The proposed study should also include details on how and which TL measurement assay (e.g., TRF, flow-FISH) would be used for comparison. With input from the Steering Committee (includes other U01 awardees) and the TRN, these detailed aims will be used to inform a collaborative Methods Comparison Study which will be developed immediately following awards, where each U01 lab will follow the exact same protocol for each method and variation will be tested for comparison. The Methods Comparison Study will be iterative, and a set of standards/guidelines will be developed using an agreed-upon cell type. Comparative assessments between methods and within method tests and retests for reproducibility will be conducted in a collaborative manner between the labs and coordinated by a Steering Committee working in collaboration with the U24 TRN. It is expected the consortium of labs will share data and findings as they emerge from the methods study within the network using an agreed upon common platform, facilitated by the U24 TRN. Shared data includes results from methods study, protocols, and their refinements.

    As the Methods Comparison Study is occurring, it will be the responsibility of the U24 TRN to convene meetings of the Steering Committee (including U01 PDs/PIs), which will require participation and collaboration from all awarded U01s, to insure transparency of methods, sharing of data, and input from community. These meetings will include an External Advisory Committee whose function will be to provide independent expert input on procedures for coordination and conduct of the measurement studies. (For details on the U24 TRN, Steering Committee, and External Advisory Committee roles and functions in this collaborative effort, see RFA-AG-19-022). This effort will scale up rapidly to build from the set of standards/best practices developed from the agreed-upon cell type to include other cell types commonly used in telomere length research (e.g., stored whole blood and buffy coat, buccal cells, saliva, and dried blood spots). Development of standards/best practices by the U01 lab consortium should differentiate between the research setting (e.g., population-scale vs. clinical study) and outline best practices, pitfalls, and limitations for each telomere length assay (e.g., measurement error, TL bias). This will require meetings where the U01 labs will be expected to develop consensus around best practices on issues such as what cell types to collect; pre-analytical factors related to sample collection, DNA extraction methods, and sample storage; assay considerations, including assay reagent, analysis method, and selection of appropriate assay controls; and issues related to batch analyses, standardization, and automation, and other considerations that may emerge from these studies. Additionally, the Steering committee should aim to achieve consensus on how to conduct comparisons between serial samples obtained from the same individual, how to treat stored samples from existing cohorts, and how many measurements over a given period of time are needed to account for normal telomere fluctuation (e.g., transient changes in TL). This will be accomplished through regular meetings to discuss progress and to evaluate and revise protocols as needed. U01 participation in these meetings is required (see Terms and Conditions below).

    Required Activity 2: Contribute to development of best practice guidelines for TL research

    The second activity is intimately connected with the first and addresses the need to develop of a set of best practice guidelines and recommendations for the field regarding biological sample collection, storage, and processing; assay parameters and laboratory methods; data analysis; limitations, and reporting requirements for telomere length measurement as they are appropriate for a given human cell type. It is expected these guidelines will be feasible and tractable for population-based research and adopted by the community and should be shared through open dialogue with the research community including meetings, and publications. These guidelines should focus on population-based studies and address cell-type(s) used, how the use of actively growing versus frozen or archived cells may affect the outcomes and limitation of the method used. The consortium of labs will contribute and offer expertise to inform discussions and refine recommendations as they are being developed. The U24 TRN will support this activity by promoting integration of a wider range of expert input from the field, including from an External Advisory Committee, as these guidelines are being developed. The U24 TRN will also support dissemination of best practices to the field at large, through enabling the sharing of data, protocols, and results from the methods comparison studies on a public platform, and through coordinating outreach to relevant scientific groups about the procedures, outcomes, and recommendations resulting from these studies and from other network activities, as well as those emerging from the field at large. Laboratories of the U01 consortium are expected to fully participate to develop these guidelines and collaborate with the U24 TRN to help meet its collective goal to establish open dialogue about optimal methods for telomere assessment, as a resource for the field and as a foundation for this rapidly evolving area of investigation. It is anticipated and acknowledged that methods for measuring TL and other biomarkers of exposure are rapidly evolving.

    Required Activity 3: Repurpose existing methods or develop new methods to enhance the use of TL measurement

    Finally, during the second and third years, after guidelines are developed for human population studies (e.g., the qPCR method), the laboratory consortium is encouraged to work collaboratively to repurpose existing or newly developed methods. Applicants are expected to submit specific aims on either how an existing telomere length measurement assay can be refined for use in population studies, or ideas for a novel assay that can be used in population health studies. Common criteria include the following: differentiate why the proposed study is superior to existing TL assays for population health (e.g., qPCR); demonstrate how it improves the sensitivity of TL measurement (e.g., single cell analysis); address assay parameters (sample collection, storage, and processing; laboratory methods; data and statistical analysis; and reporting requirements, etc.) and address any limitations (e.g., cell type, sensitivity). As each U01 applicant will submit specific aims for this activity, the choice of which assays will be developed will be informed by knowledge gained from activities 1 and 2, input from the Steering Committee including all U01 PDs/PIs, coordinated by the U24 Telomere Research Network (TRN) (RFA-AG-19-022) and based on assay feasibility for population studies. As with Activity 1, each U01 will conduct its own analyses, and share protocols and data with the consortium, facilitated by the TRN.  

    Resources for Applicants

    Information about the NIEHS/NIA Workshop on Telomeres as Sentinels for Environmental Exposures, Psychosocial Stress, and Disease Susceptibility is available at the following links:

    Meeting book: https://www.niehs.nih.gov/about/events/pastmtg/2017/telomeres/meeting_book_508.pdf

    Bibliography:  https://www.niehs.nih.gov/about/events/pastmtg/2017/telomeres/telomere_bibliography_508.pdf

    Workshop report: https://www.niehs.nih.gov/about/events/pastmtg/2017/telomeres/telomere_meeting_report_508.pdf

    Responsiveness Criteria

    Applicants deemed to be non-responsive will not proceed to review. The following are considered non-responsive to this FOA:

    • Applicants that do not demonstrate expertise in gold standard (e.g., TRF) and high-throughput telomere length measurement techniques
    • Applications that propose optimal telomere length methods comparisons studies that are not feasible for population health studies

    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.

    Clinical Trial?

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

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIA and NIEHS intend to commit a combined total of $1.417 million across RFA-AG-19-022 and RFA-AG-19-023 to fund 3-4 U01 awards and one U24 award.

    Award Budget

    Application budgets are limited to $200,000 in direct costs per year.

    Award Project Period

    The scope of the proposed project should determine the project period. The maximum project period is 3 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)

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

    Other

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

    Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply.
    Non-domestic (non-U.S.) components of U.S. Organizations are  eligible to apply.
    Foreign components, as defined in the NIH Grants Policy Statement, are  allowed.

    Required Registrations

    Applicant Organizations

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

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • System for Award Management (SAM) (formerly CCR) – 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. 
    • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
    • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

    2. Cost Sharing

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

    3. Additional Information on Eligibility
    Number of Applications

    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:

    • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
    • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
    • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms 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 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.

    For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

    Letter of Intent

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

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

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

    The letter of intent should be sent to:

    Lis Nielsen, Ph.D.,
    National Institute on Aging (NIA)
    Michelle Heacock, Ph.D.,
    National Institute of Environmental Health Sciences (NIEHS)
    Email: NIATelomeresFOAs@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

    Describe plans for accomplishing the three objectives of the Methods Comparison Project:

    1) To conduct a Collaborative Methods Comparison Study. The U01 applicants should provide a detailed description of how they would conduct an optimal methods comparison study that includes approaches appropriate for population-based studies (e.g., qPCR) that could inform standards for the field. These details for TL assessment in actively growing versus frozen or archived cells (selecting cells commonly used for TL measurement in population-based studies; e.g., stored whole blood and buffy coat, buccal cells, saliva, and dried blood spots) should include: sample collection; cell preparation; DNA extraction method and sample storage conditions; assay parameters, including reagents; analysis methods, including statistical approaches; selection of reference standard and controls; issues related to batch analyses; standardization and automation considerations; and reporting requirements. Details should include plans to use an appropriate TL measurement assay (e.g., gold standard assays, TRF or flow-FISH) for comparison. Applicants should describe how they will work with the Steering Committee and the TRN to incorporate key aspects of each of the U01 optimal methods comparison study into the collective TL Comparison Methods Study to be conducted by each of the U01s. Applicants should describe plans for sharing protocols and data with the consortium (e.g., best practices, quality control, biostatistics, timeline for sharing, etc.) during the methods development process. A description should be provided of how the applicant plans to contribute to working collaboratively to inform best practices on issues such as what cell types to collect; pre-analytical factors related to sample collection, DNA extraction methods, and sample storage; assay considerations, including assay reagent, analysis method, and selection of appropriate assay controls; and issues related to batch analyses, standardization, and automation, and other considerations that may emerge from these studies. 

    2) Contribute to Development of Best Practice Guidelines for TL Research. The U01 applicants should describe plans for coordination and sharing of their data protocols, and results. Applicants should describe how they will participate in developing these guidelines and collaborate with the U24 TRN to help meet its collective goal to establish open dialogue about optimal methods for telomere assessment, as a resource for the field and as a foundation for this rapidly evolving area of investigation.

    3) Repurpose existing methods or develop new methods to enhance the use of TL measurement. The U01 applicants should provide a description on how an existing telomere length assay can be refined for use in population studies, or ideas for a novel assay that can be used in population health studies. The description should differentiate why the proposed study is superior to existing TL assays for population health (e.g., qPCR); address assay parameters (sample collection, storage, and processing; laboratory methods; data and statistical analysis; and reporting requirements, etc.) and address any limitations (e.g., cell type, sensitivity).

    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, with the following modification:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • NIH expects the sharing of study data from both the TRN and the Methods Comparison Projects in a timely manner, and with appropriate privacy and confidentiality protections to facilitate further research, reuse of data, and replication. Awardees will be expected to implement a Resources and Data Sharing Plan consistent with achieving these program goals.
    • In addition, NIH encourages sharing of software and code that are developed or modified to accomplish aims of this program. The goals of software sharing under this program include 1) broad availability to biobehavioral, biosocial, and biomedical researchers, research institutions, and government health care systems; 2) terms that permit the dissemination and/or commercialization of enhanced or customized versions of the software, or incorporation of the software or components of it into other software packages; and 3) terms of software availability that include the ability of individuals outside the applicant institution and its collaborating organizations to modify the source code and to share modifications with others. If software is developed with support from this program, awardees and their sub-contractors are expected to implement software sharing plans consistent with achieving the goals of this program.

    Appendix:

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

    PHS Human Subjects and Clinical Trials Information

    When involving NIH-defined human subjects research, clinical research, and/or 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

    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. 

    Foreign Institutions

    Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

    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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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.

    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. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

    In addition, for applications involving clinical trials:

    A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

    Overall Impact

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

    Scored Review Criteria

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

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

    How well does the proposed methods comparison study address the needs for TL measurements in population health (i.e., qPCR) research? If the study were to be used, how does it address development of guidelines for TL measurement that can be used by population health research to understand how TL can be used as sentinel of detrimental exposure effects across the lifespan, age related response, and adverse health outcomes?

    For activity 3, how well does the proposed study augment existing and/or develop novel and robust TL measurement assays to address the needs in population health research?  If the method were to be used, is it tractable for use in population health (e.g., feasible, easy to obtain cell types, high-throughput potential)?

    In addition, for applications involving clinical trials

    Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?  For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?  

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

    Do the investigators have the appropriate expertise in high throughput TL measurement, biostatistics, and molecular and telomere biology to undertake the type of collaborative methods development required by this RFA?

    In addition, for applications involving clinical trials

    With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?    

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

    Is there a strong potential for the proposed methods study to inform guidelines that can be used for TL measurements in population health studies? 

    Will the proposed study make significant contributions to developing guidelines for TL measurements?

    Is there strong potential for the proposed research to refine existing or develop novel TL measurement approaches so TL measurement in population health studies can be improved by increasing sensitivity (e.g., high resolution at the base pair or individual telomere level)?

    In addition, for applications involving clinical trials

    Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?   

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

    Are the proposed studies supported by preliminary data? Will the study methodologies proposed enable development of recommendations for use of qPCR to measurement TL in population health studies seeking to understand if telomeres can act as a sentinel of detrimental exposure effects across the lifespan, age related response, and adverse health outcome? Will the methods that propose to refine/augment existing or to develop novel TL measurement assays improve the ability to measure the telomere (e.g., by increasing sensitivity and or resolution at the base pair/individual telomere level, or include companion biomarkers to improve biological context)? Are the proposed studies and approaches appropriate, well-matched to the nature of the project, and sufficient to enable the development of guidelines and improved telomere length measurements?

    In addition, for applications proposing clinical trials

    Does the application adequately address the following, if applicable

    Study Design

    Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

    Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

    Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

    Data Management and Statistical Analysis

    Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?    

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

    In addition, for applications involving clinical trials
    If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

    Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

    If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

    If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure? 

    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.

    Study Timeline

    Specific to applications involving clinical trials

    Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

    Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?   

    Trans-Network Interactions

    What is the potential of the proposed research team for a meaningful synergy with other network members (i.e., other U01s, the TRN [U24]) and the outside telomere research community? Would the proposed studies benefit from collaborative interactions with the other U01s, TRN, and outside telomere research community? Will the application allow flexibility in collaboration with the other U01s, TRN, and outside telomere research community? Will the investigators bring valuable areas of expertise to the TRN that will maximize flexibility toward reaching the goals of this announcement?        

    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the six 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 six 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 Children 

    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 children 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

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations

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

    Applications from Foreign Organizations

    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.

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

    Authentication of Key Biological and/or Chemical Resources:

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

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

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Environmental Health Sciences, 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:

    • 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.
    • Will receive a written critique.

    Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

    Applications will be assigned on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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

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

    Section VI. Award Administration Information
    1. Award Notices

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

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

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

    Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

    ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/

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

    Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

    Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).     

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

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

    The administrative and funding instrument used for the TL Methods Comparison and optimization Projects 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. Awardee will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

    Definitions

    Methods Comparison Project: One of the U01 awards funded under RFA-AG-19-023 working on the Methods Comparison Study.

    Telomere Research Network (TRN): The U24 award funded under RFA-AG-19-022 and all participants in activities supported by the U24. TRN is expected to expand to engage and include other investigators in the broader field over time, through participation in workshops, pilot research programs, and other activities.

    Methods Collaboratory: The total collection of projects and staff that encompass the two companion FOAs: RFA-AG-19-022 and RFA-AG-19-023.

    Steering Committee: The main governing board of the Telomere Research Network comprised of PDs/PIs and NIH Project Scientists from each U01 award and the U24 award as well as additional investigators and NIH staff as appropriate. The Steering Committee may establish subcommittees as deemed appropriate.

    External Advisory Committee (EAC): A panel of four to six senior scientists with relevant expertise who are not PD(s)/PI(s) of a project involved in the Telomere Research Network that will provide expert input to the Steering Committee about the design and conduct of the methods comparison study.

    Network Governance

    The awards funded under this FOA and the companion FOA will be cooperative agreements (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close interaction with the NIH and with the other awardees will be required to accomplish the goals of this program.

    A Telomere Research Network Steering Committee will be established to address issues that span the TRN and all Methods Comparison Projects, including providing input into the processes of the projects, and assisting in dissemination of all of the deliverables named above. Principles of governance will be established at the initial meeting.

    Areas of Responsibility

    The U01 PD(s)/PI(s) will have the primary responsibility for:

    • Defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of TL measurements conducted.
    • Assuming accountability to the applicant organization officials and to the NIH for the performance and proper conduct of Methods Collaboratory research in accordance with terms and conditions of the award.

    All Program Director(s)/Principal Investigator(s) of the TRN will have the primary responsibility for:

    • Overseeing the budget and activities of the award, as detailed, above.
    • Cooperating with other U01 and U24 investigators and NIH Staff, as appropriate, in the design and conduct of protocols, analysis of data, and reporting of results of research undertaken by the Methods Collaboratory.  This includes, but is not limited to:
    • Providing goals and estimated costs for procedures and protocols.
    • Sharing data, updated protocols and other research resources generated through the U01 award.
    • Promoting and coordinating cross-U01 and TRN scientific collaboration.
    • Ensuring training of study site personnel as needed for standardization of collaborative protocols across sites and for accurate and timely data measurements.
    • Facilitating the formation of and participating in appropriate Working Groups to promote exchange of preliminary findings, inconsistencies/or validation of protocols, and ideas across the Methods Collaboratory.
    • Interacting and complying with requests for information from the Steering Committee and other sub-committees as appropriate.
    • Participating in annual PD/PI scientific meetings, and monthly committee calls organized by the TRN, as relevant.
    • Accepting and implementing all scientific, practical, and policy decisions approved by the Steering Committee to the extent consistent with applicable grant regulations.
    • Serving on the Steering Committee (for details, see "Areas of Joint Responsibility" below).
    • Providing information to the NIH Program Directors and Project Scientists concerning progress by submitting annual progress reports in a standard format.
    • Complying with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events.

    NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

    One or more NIA/NIEHS Program Directors will be substantially involved in the Methods Collaboratory as NIH Project Scientists. NIH Project Scientists will have scientific and programmatic involvement that is above and beyond the normal stewardship role in awards.  NIA/NIEHS Project Scientist(s) will have the following responsibilities to all Methods Collaboratory awardees:

    • Have substantial involvement to guide, coordinate, and participate in the conduct of the Methods Collaboratory activities.
    • Attend and participate in all Steering Committee and subcommittee meetings.
    • Coordinate and facilitate the interactions among the awardees under this U01 cooperative agreement.
    • Serve as a liaison between the Steering Committee, the Methods Collaboratory, the Methods Comparison Projects, the TRN, the NIH and other federal agencies as needed.
    • Facilitate and coordinate the exchange of information and interactions between Methods Collaboratory awardees to support collaborative efforts.
    • Participate in organizing and coordinating TRN Scientific meetings as required.
    • Advise on the design of research activities, availability of resources, and/or management and technical performance of projects, as appropriate.
    • Participate as collaborators to the U01 investigators in some shared activities, if appropriate.
    • Assist in avoiding unwarranted duplications of effort across the Methods Collaboratory and TRN.
    • Evaluate the adherence of U01 awardees to any approved data sharing plans or intellectual property plans.

    Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NIH reserves the right to adjust funding, withhold, suspend, or terminate the support to those Methods Collaboratory awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance. The NIH Program Official will be responsible for monitoring the level of performance and making recommendations for any corrective actions.

    Areas of Joint Responsibility include:
    A Steering Committee will serve as the governing board for the Methods Collaboratory.

    The Steering Committee will have primary responsibility for:

    • Overseeing the overall organization of the Methods Collaboratory initiative and for reviewing its research goals. Evaluating the adherence of U01 awardees to any approved data sharing plans or intellectual property plans.
    • Developing the appropriate structure of Working Groups to promote the exchange of experiences, protocols, novel research findings, etc. across the Methods Collaboratory.
    • Establishing advisory committees and subcommittees, as necessary, to serve the Steering Committee and the U01 awardees.
    • Making recommendations for re-directing the Methods Collaboratory's focus in order to accommodate new scientific opportunities and directions.
    • Sharing and reviewing annual progress among the components of the Methods Collaboratory.
    • At a minimum, the Steering Committee will be composed of one Principal Investigator from each of the Methods Comparison Projects, the NIH Project Scientist for each Methods Comparison Project, the Director (contact PD/PI) of the TRN, the NIH Project Scientist for the TRN and other representatives from NIA and NIEHS, as necessary. All members are expected to actively participate in all Steering Committee activities. Principles of governance will be established at the initial meeting. The PD/PI for each of the U01 projects and the PD/PI for the TRN will each have a vote.  NIH staff will have one vote. Other NIH staff members may participate in Steering Committee meetings as non-voting members.
    • The PD/PI of the U24 TRN will serve as chair of the Steering Committee for the first award year. Thereafter, a Steering Committee Chair will be elected every twelve months from amongst the Steering Committee members by the committee. An individual may continue serving as Chair for more than one year if all committee members agree. NIH staff cannot serve as Steering Committee Chair. NIH staff will serve as ex-officio Secretary of the Steering Committee. 
    • The Steering Committee may establish subcommittees as needed to advance Methods Collaboratory goals.
    • In the event that PD(s)/PI(s) cannot agree on critical aspects of the Methods Collaboratory, such as common protocols, then the Steering Committee, in consultation with NIH Program Staff, will vote on a recommendation for how to proceed. NIA/NIEHS Staff will have final authority to implement proposed recommendations. All activities must comply with NIH, DHHS, and Federal Guidelines.
    • Other guidelines for the Steering Committee, such as a quorum and frequency and type of meetings (in-person, remote), will be determined at its initial meeting. It is anticipated that the Steering Committee will meet at least once per month by teleconference.
    • After the first meeting, the Steering Committee will develop governing by-laws for publications, data sharing, data storage, collaborations, etc. After each meeting, the EAC can meet in closed session and make a confidential report to the Steering Committee.
    External Advisory Committee (EAC)

    An External Advisory Committee will be established for years 1-3, to provide expert input to the Network and NIH partners about the design and conduct of the collaborative Methods Comparison study. The members with relevant expertise will be nominated by the U24 and U01 PIs, NIH staff, and will be selected and invited by the Steering Committee. The EAC is expected to have 4-6 members; however, the membership may be enlarged on an ad hoc basis as needed. The EAC will meet with all project leads at the kick-off meeting, to be scheduled in the fall of 2019, and again once a year in conjunction with an annual in-person Steering Committee meeting coordinated by the TRN. The function of the EAC will be to provide external input on the design, conduct and progress of the methods comparison study and development of recommendations for the field, including changes, if any, which would benefit the program.

    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 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.

    3. Reporting

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

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

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, 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 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)

    Lis Nielsen, Ph.D.
    National Institute on Aging (NIA)
    Telephone: 301-496-3136
    Email: nielsenli@nia.nih.gov

    Michelle Heacock, Ph.D.
    National Institute of Environmental Health Sciences (NIEHS)
    Telephone: 984-287-3267
    Email: heacockm@niehs.nih.gov

    Peer Review Contact(s)

    Leroy Worth, Ph.D.
    National Institute of Environmental Health Sciences (NIEHS)
    Telephone: 984-287-3340
    Email: worth@niehs.nih.gov

    Financial/Grants Management Contact(s)

    Karen Molina
    National Institute on Aging (NIA)
    Telephone: 301-827-8226
    Email: karen.molina@nih.gov

    Lisa Archer Edwards
    National Institute of Environmental Health Sciences (NIEHS)
    Telephone: 984-287-3258
    Email: archer@niehs.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.

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