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.

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

Epidemiological studies of long-lived individuals have provided insight into the interactions between morbidity, mortality, and survival to older age and have revealed the existence of a strong relationship between exceptional longevity and exceptional health span. For example, centenarians show delayed onset of age-related disabilities and morbidities such as cardiovascular disease and Alzheimer’s disease. These findings are consistent with the concept that aging mechanisms influence both longevity and the development of multiple age-related conditions. Identifying factors that influence such mechanisms could facilitate the identification of potential therapeutic targets to enhance human health span.

Individuals with exceptional health and life span are believed to reflect combined influences of environmental and multiple genetic variants that influence health and life span. Genome-wide association studies (GWAS) of exceptional human longevity and healthy aging have identified several variants associated with longevity and health span, such as APOE2 and FOXO3A. While these variants can serve as a starting point for efforts to identify therapeutic targets, strategies based on genetics alone have substantial limitations. Many gene products have multiple targets that interact with each other and with multiple genes. The relationships of genetic variants to expression profiles of RNA, proteins and metabolites that influence longevity and health are complex. Thus, there is a need for multi-omics/integrative approaches (i.e., omics profiles) which could yield better predictors of healthy aging phenotypes than can be found based simply on individual gene variants, as well as guide the assessment of drugs targeted at specific molecules. Furthermore, there is a need for phenomic approaches to assess the relationship of genetic factors and omics profiles to a wide range of aging related outcomes (e.g., to distinguish between factors that affect only a single age-related condition or have opposing effects on different conditions versus factors with more consistent beneficial effects).

Another important consideration for future analyses is the integration of findings by cross-species comparative genomic analysis. Preliminary studies conducted in species with widely varying life spans suggest that comparative multi-omics analyses of proteins, metabolites, and gene expression profiles from long-lived vs. short-lived species of birds, primates, and rodents could assist in the discovery of molecular factors and tissue-specific molecular pathways influencing life span and health span. In this regard, placing the findings from model organisms into the context of human cohorts is of crucial importance to the identification of conserved biological pathways that may extend health and life span across species.

The advent of technologies has enabled the collection of large omics data sets including genome, transcriptome, proteome, metabolome and phenome. Several population cohorts that include centenarians and exceptionally long-lived individuals are making use of the advances in genomic/proteomic technologies to generate large data sets on omics. These datasets, if examined by multidimensional/integrative approaches (including findings from comparative biology) uniting top-down omics data with bottom-up biological networks in a synergistic fashion, could untangle the interdependence of regulatory layers represented by various omics data and their influence over the global biological networks/pathways and eventually help to identify key factors underlying healthy aging and novel therapeutic targets to enhance health span.

This FOA invites the submission of a single cooperative agreement and phased innovation UH2/UH3 to identify omics profiles associated with protection against multiple aging conditions and with exceptional health span and refine strategies for utilizing these profiles in therapeutics development. Applications submitted in response to this FOA should include an interdisciplinary research team with expertise in epidemiology, aging biology, comparative biology, genetics, various types of omics methods and bioinformatics. Specifically, this FOA will support multiple omics measurements (e.g., transcriptomics, proteomics, metabolomics) from the same individual and from multiple tissues from extensively phenotyped cohorts with substantial numbers of long-lived individuals and controls. It will also: 1) harmonize and extend the use of existing phenotypic data from these studies to apply phenomics to transcriptomic, proteomic, metabolomic findings; 2) select animal model species or strains with varying life spans for comparative omics studies and identify potential determinants of species differences in longevity and rates of disease development; 3) develop appropriate computational and analytical tools to identify omics profiles associated with exceptional longevity and healthy aging; 4) apply translational bioinformatics approaches and leverage existing publicly available drug signatures databases to identify molecules that could produce profiles associated with exceptionally healthy aging; and 5) exchange data with other NIH/NIA-supported related omics activities and other public-private partnerships (e.g., Trans-Omics for Precision Medicine (TOPMED), Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD)) for data harmonization and analysis.

Limited whole genome sequencing analysis on extreme phenotypes for rare variant analysis may also be included in the specific aims when sequencing data are not available in the assembled longevity cohort(s) and required to conduct the proposed integrative analysis.

Investigators responding to this FOA must address plans for both the UH2 and UH3 phases in a single application as described below. The UH2 phase (up to 2 years in duration) will be a milestone-driven pilot/innovation phase examining essential methodologies and resources needs such as omics data and bio-specimens, development and/or refinement of computational tools for integrative data analysis. Upon successful completion of established milestones, the project will transition to the UH3 phase (up to 3 years in duration with a total project period of 5 years) focusing on optimization and full-scale implementation of integrative analyses based on the resources developed and data acquired during the UH2 phase.

Phase 1 (UH2) The UH2 phase should include the following types of research activities:

• Evaluate resource needs for genetic and omics data including well defined and characterized phenotypic data and biospecimens collected from cohorts with substantial number of long-lived individuals and appropriate controls. This includes harmonization of data, as needed.
• Assess needs for generation of limited omics data (e.g., type of omics, feasibility of using stored tissue specimens) and limited whole genome sequencing (WGS) data.
• Establish a data management/computational infrastructure to assemble existing data and support integrative analyses of multi-omics datasets including phenotypic data (e.g., eHR data bases).
• Collection of biospecimens (whole blood, cells, muscle biopsies) on existing cohorts and long-lived, non-human species for limited omics data generation.
• Develop appropriate or refine existing computational methods for rare variant and integrative multi-omics analyses including orthology and paralogy assessment tools for comparative omics studies of species or strains of varying life spans.

Phase 2 (UH3) - In Phase 2 and based on results obtained during Phase 1, the awardee will:

• Generate new omics data from existing cohorts of long lived individuals and non-human species. The awardee may use funds to generate limited whole genome sequencing data on cohorts with extreme phenotypes for rare variant analysis.
• Validate and further refine (as needed) newly developed computational tools for implementation on large data sets.
• Implement computational methods/analytical tools on harmonized large data sets for data extraction, predictive modeling and integrative analysis to identify protective profiles associated with exceptional healthy aging.
• Apply chemoinformatic drug screening tools including Connectivity Map Analysis (CMAP) on targets based on the identified protective mechanistic pathway(s).
• Strategize pilot translational studies (e.g., in vitro systems) on novel molecules that influence metabolic pathways associated with exceptional life and health span identified by drug screening tools

Transition from the UH2 to the UH3 phase:

• An initial cooperative agreement award for up to 2 years will be made for the UH2 phase and completion of established milestones (proposed by the investigator and established in collaboration with NIA staff) will be used to assess potential transition from the UH2 to the UH2 phase.
• Prior to the end of the UH2 phase, awardees will be expected to submit a package requesting transition to the UH3 phase. This transition package should include a progress report describing the achievements of the UH2 phase based on the established milestones and plans for the UH3 phase considering the activities successfully completed during the UH2 phase.
• Transition packages will be reviewed by NIA program staff.

Criteria to determine whether the award will transition from the UH2 phase to the UH3 phase will include:

• Successful completion of established milestones during the UH2 period of the project.
• Demonstration of the feasibility of established data management/computational infrastructure to support analysis of large data sets and integrative multi-omics data during the UH3 phase.
• Curation and harmonization of omics data from cohort studies of long-lived individuals and controls that will enable proposed UH3 activities.
• Collection and appropriate storage of new biospecimens for limited data generation (omics or WGS) for further analysis during UH3 phase.
• Complete evaluation of existing computational tools for integrative analysis and any further refinement/validation of these computational tools.
• The awardee should have planned for new methodologies (if necessary) for data integration and predictive modeling, including rare variant search in the collected cohorts and integrating genetics with the multi-omics data for identifying target(s).
• Extent to which UH2 pilot/innovation phase activities support the aims of the UH3 phase, including the availability of multi-omics data from the same individual and from multiple tissues in a substantial number of long-lived individuals and controls to identify potential omics profiles associated with exceptionally healthy aging.
• Compliance with sharing of resources and/or data generated by the UH2/UH3 with NIH Sharing policies for NIH-Funded Research Resources and Genomic Data Sharing (GDS) will be an important criterion for transition from UH2 to UH3, in addition to the established milestones.

Research projects focusing primarily on generating or analysis of single omics data or sequencing data and independent analysis of these data sets will be considered non-responsive to this FOA. Although limited studies to generate multi-omics data will be encouraged and supported by this FOA, studies focused solely on the generation of new WGS data in cohorts is outside the scope of this FOA. This FOA will not accept clinical trials.

This FOA addresses topics that complement those of other NIA/NIH FOAs on integrative data-driven approaches for novel target and biomarker discovery, next-generation animal models development and drug repurposing for Alzheimer’s carried out within NIA’s four large, open-space consortia: AMP-AD, M2OVE-AD, MODEL-AD and Resilience-AD (RFA AG17-061), as well as NIA’s translational bioinformatics program for drug repositioning and combination therapy development for Alzheimer’s and related dementias (PAR-17-032) and NHLBI’s TOPMED program (RFA-HL-18-020). As such, exchange of ideas and information through meetings or other venues between the awardee supported through the present FOA and awardees of the above mentioned FOAs will be encouraged, and NIA program staff will facilitate these interactions as part of their role in this cooperative agreement.

A webinar is planned to provide prospective applicants the opportunity to receive information and ask questions about the scientific scope of this announcement and technical details for applying. Please refer to the link (https://www.nia.nih.gov/research/dgcg/integrative-omics-enhance-therapeutics-development-healthy-aging) for details on the webinar (time and date) and registration.

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

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

Higher Education Institutions

• 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)

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.

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.

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

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

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

• 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).

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.

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.

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:

Nalini Raghavachari, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6942
Fax: 301-402-1784
Email: nraghavachari@mail.nih.gov

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

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

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. Applicants should include travel funds for an annual in-person meeting in the Washington, D.C./Bethesda area with all the PIs involved in the study.

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

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

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

Specific Aims: Describe and clearly demarcate the specific aims for both phases (UH2 and UH3) of the proposed project. Provide justification for generating WGS and omics data by assessing the existing resources in the assembled cohorts in UH1 Phase to conduct the analysis in UH2 phase. Evaluate the efficiency of available computational tools for integrative data analysis on genetics and multi-omics data and fine tune the existing tools and describe the need for developing newer methodologies.

Research Strategy: Provide a rationale to justify the significance of the selected methodologies and computational strategies proposed for identifying profiles associated with exceptional aging process. Describe the goals and research approach with milestones for both phases of the proposed project and distinguish clearly between the two phases. Describe any innovative aspects of the approach.

Applications must include milestones specific to the proposed project that will be reached by the end of the UH2 and UH3 phase.  Metrics to assess achievement of milestones should be fully explained in the application. 

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:

In keeping with the goal of the NIA/NIH to enhance the transparency of reporting and enable reproducible and translatable discovery research, awardees will be expected to make all data, analytical methods, network models and research tools available to the broad scientific community prior to publication.

Consistent with achieving the goals of the NIA and this program, it is expected that all applications will meet the following conditions:

• All datasets used/generated on the project (such as data about clinical phenotypes and high-dimensional omic data, including genomic, proteomic, and metabolomic data generated from human samples and animal models) will be made accessible and reusable by qualified individuals other than the original data generators to enable data analysis and interpretation.
• All analytical methodologies will be made fully reproducible and transparent so that results can be vetted, and existing analysis techniques quickly applied to new application areas.
• All models of biological systems and networks will be made open to users such that theoretical predictions can be rapidly validated experimentally.
• All biological samples used to generate data with this award will be made available to awardees of other related initiatives such as AMP-AD, and other qualified investigators.
• Timeliness of sharing of resources and/or data generated by the UH2/UH3 will be an important criterion for transition from UH2/UH3 in addition to the established milestones.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

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.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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.

In order to expedite review, applicants are requested to notify the {IC} Referral Office by email at ramesh.vemuri@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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

Only the review criteria described below will be considered in the review process. 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.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is 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?

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 composition of the investigative team reflect the multidisciplinary expertise needed to achieve the proposed aims?

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 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 computational strategies for integrating multi-omics data and projected time line for the project sufficient to achieve the research goals of this FOA?

Has the applicant described in sufficient detail and adequately justified their selection of cohorts of long-lived individuals and appropriate controls for the proposed study?

Has the applicant described in detail the availability of multi-omics data (from the same individual) or bio-specimens for generating new data and methods for assessing data quality on these subjects and demonstrated that access to these resources have been granted (i.e., letters of support)?

Are the proposed analytical tools adequate for integrating data to identify protective omics profile to enhance health and life span?

Has the applicant provided details on the need for new computational analytical strategies and has provided a strong rationale for the planned approaches for data integration and analysis for the identification of protective omics profiles.

For the identified omics profiles, are the criteria for evaluating their potential utility as a basis for developing therapeutic target ID strategies appropriate? If de-novo pilot studies are proposed, are their contributions to target identification clearly explained, and are their design and statistical methods adequate?

Are the potential limitations on the proposed approaches and possible alternative strategies adequately addressed?

Are plans reasonable and described in adequate detail with regard to exchange of data and public-private partnerships (e.g., Trans-Omics for Precision Medicine (TOPMed), Accelerating Medicines Partnership- Alzheimer’s Disease (AMP-AD) for data harmonization and analysis?

Are the milestones specified by the applicant realistic and appropriate for the proposed project? Will the proposed project lead to novel methodologies that could identify omics profiles associated with health and life span?

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

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

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.

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.

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

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). In addition, reviewers will consider whether:

    All datasets used/generated on the project (such as data about clinical phenotypes and high-dimensional omic data, including genomic, proteomic, and metabolomic data generated from human samples and animal models) will be made accessible and reusable by qualified individuals other than the original data generators to enable data analysis and interpretation.

    All analytical methodologies will be made fully reproducible and transparent so that results can be vetted and existing analysis techniques quickly applied to new application areas.

    All models of biological systems and networks will be made open to users such that theoretical predictions can be rapidly validated experimentally.

    All biological samples used to generate data with this award will be made available to awardees of related initiatives, such as AMP-AD and to other qualified investigators.

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, 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 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 Advisory Council on Aging. 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.

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.

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.

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.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 https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/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 https://www.hhs.gov/ocr/about-us/contact-us/index.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 Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project, 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:

• Defining the overall research objectives and approaches of the UH2/UH3 project.
• Determining computational analytical and experimental approaches, designing protocols, setting project-specific milestones in collaboration with the awardee and overseeing conduct of analyses and experiments.
• Overseeing and coordinating the effort of the multidisciplinary team and participating Institutions and ensuring their optimal interactions and integration in the conduct of research activities.
• Ensuring compliance with NIH policies, including protection of human subjects.
• Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIA support, including the assigned cooperative agreement award number.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• The NIA Project Scientist will interact scientifically with the research team and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the research team's objectives and research activities, presenting experimental findings to the research team from published sources or from other relevant sources, participating in the design of experiments agreed to by the research team, participating in the analysis of results, and advising in management and technical performance.
• The NIA Project Scientist will facilitate interaction with other NIH supported activities on similar studies involving integrative multi-omic analyses for exchange of information, ideas tools and data resources.
• The Project Scientist will be a member of the research governing body. In all cases, the role of NIA will be to assist and facilitate and not to direct activities.
• Additionally, a NIA Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.

Areas of Joint Responsibility include:

Research Governing Body:

• The Steering Committee will serve as the research governing body for the UH2/UH3 project, consisting of the leadership of the UH2/UH3 project and NIA staff (one voting member).
• The research governing body will be chaired by one of the UH2/UH3 PDs/PIs.
• The research governing body members will meet regularly to review and monitor progress, plan and design research activities, and establish priorities. Meetings may occur as regularly scheduled teleconferences and include at least 1 in-person meeting each year in Bethesda, MD over the course of the UH2/UH3 project period.
• The PI(s)/PD(s) will be responsible for scheduling the teleconferences and in-person meetings, as well as for preparing concise minutes from teleconferences and in-person meetings. The meeting minutes will be distributed to the NIA Program Office and to research team members within one week of the meeting.

External Advisory Board:

Awardee may elect to have an External Advisory Board that can provide guidance as needed to the project, with subject matter expertise to supplement or complement the areas of expertise of the research team members. This information should be included in the Approach section of the Research Strategy. The application should identify the expertise appropriate for the monitoring board and the number of members.

Applications should NOT recommend individuals or provide biographical sketches of proposed monitoring board member

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the

award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the award governing body 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.

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.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten 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

Nalini Raghavachari, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6942
Email: nraghavachari@mail.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: ramesh.vemuri@nih.gov

Lesa McQueen, M.Sc.
National institute on Aging (NIA)
Telephone: 301- 402-7738
Email: McQueenL@nia.nih.gov

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

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