National Institute on Aging (NIA)
August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
This Funding Opportunity Announcement (FOA) supports concerted efforts that take a multipronged, team-science strategy and apply high-throughput, genome-wide approaches to systematically discover and characterize functional genomic and epigenomic elements and elucidate and validate their functional roles and mechanisms of action underpinning the heterogeneity, pathogenesis, and progression of Alzheimer’s disease and related dementias (AD/ADRD).
February 25, 2020
June 1, 2020
July 1, 2020
No late applications will be accepted for this Funding Opportunity Announcement. All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
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.
This Funding Opportunity Announcement (FOA) is issued as an initiative tied to activities outlined in the National Plan to Address Alzheimer's Disease 2019 Update (See Strategy 1.B). The National Plan is updated on an annual basis in response to the National Alzheimer's Project Act (NAPA) Public Law 111-375. The NIA-funded Alzheimer’s Disease Sequencing Project (ADSP) aims at identifying genes and genetic variants associated with risk of and protection against Alzheimer’s disease (AD). The overarching goals of the ADSP are to: (1) identify new genes and variants involved in Alzheimer’s disease and Alzheimer's disease-related dementias (AD/ADRD), (2) identify gene alleles and allelic variants contributing to increased risk for or protection against the disease, (3) provide insight as to why individuals with known risk factors escape developing AD, and (4) identify potential avenues for therapeutic approaches to and prevention of the disease.
Genome-wide association studies (GWAS) by the ADSP and the International Genomics of Alzheimer's Project have identified more than fifty loci associated with Alzheimer’s disease. However, progress toward understanding disease mechanisms has been limited due to the difficulty in assigning molecular function to these GWAS loci. A single GWAS locus typically spans several genes and has multiple variants that are equally associated with the disease due to linkage disequilibrium. It is difficult to identify which is the causal gene/variant in the linkage region. Even after determining causal variants, understanding their functions and the cellular states and processes in which they operate is a major challenge. Moreover, the majority of the AD-associated genetic variants lie outside of the protein coding regions of the genome. These non-coding variants affect genetic and epigenetic regulation of gene expression that is highly dependent on cellular context. Decoding the function of noncoding variants further challenges the interpretation of GWAS loci.
Recent genomic studies have identified a suite of structurally and functionally diverse non-coding RNAs (ncRNAs) that are implicated in AD pathophysiology. A vast repertoire of ncRNAs displayed by the human genome has been discovered and classified, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNA, small nucleolar RNAs (snoRNAs), and piwi-interacting RNAs (piRNAs). Growing evidence demonstrates that ncRNAs play important roles in the pathophysiology of AD by epigenetic regulation of gene expression, messenger RNA (mRNA) translation, and protein production. However, the specific functions and mechanisms of action of the vast majority of AD-related ncRNAs remain to be discovered. Although there is a growing interest in exploring ncRNA-based therapeutics, their pertinence as potential biomarkers and therapeutic targets remains uncertain because their roles in the pathophysiology of AD/ADRD are largely unknown. Obtaining a deeper understanding of these non-coding RNAs is a new area of interest for the genetics of AD/ADRD.
AD is a complex polygenic disease with genetic, cellular, and pathologic heterogeneity. Recent studies using a variety of clinical and neuropathological measures indicate that the disease may be comprised of a spectrum of difficult-to-discern endophenotypes, each with its own genetic and clinical signatures. Endophenotypes reflect the way that a disease is manifest in subgroups of individuals. Each subgroup may have unique biomarkers, such as specific patterns of changes in tau or amyloid beta. It is highly likely that genomic variants are strongly associated with AD/ADRD-related endophenotypes in early disease stage, but the genetic drivers and the underlying mechanisms are largely undefined. Characterizing clinically relevant endophenotypes for subjects with AD/ADRD will help to deconvolute mechanistic complexity and cellular heterogeneity. Associating endophenotypes with the function of genes and variants may lead to a better understanding of disease subtypes, which is crucial to the identification of appropriate therapeutic targets for better treatment.
Functional interpretation of genetic variations has been challenging historicallyand remains a persistent bottleneck in genetic studies of complex diseases. This is hindering the discovery of genetic-based targets for therapeutics. To connect genetic variants to downstream effectors and functions, a number of issues need to be addressed, including the need to: (1) pinpoint causal variants that affect disease susceptibility and/or progression, (2) characterize the molecular and biochemical effect of these variants and identify the target genes on which these variants act and the cell types and states in which these variants operate, (3) determine links to heterogeneous cellular and pathologic mechanisms, and (4) identify genetic drivers underlying AD endophenotypes that are clinically relevant but difficult to ascertain. In particular, understanding non-coding variants and elucidating their causal mechanisms remain a momentous challenge. As in many other complex diseases, functional studies in AD/ADRD aimed at delineating the causal genetic variants and biological mechanisms underpinning the observed statistical associations have lagged far behind the discovery of association signals.
There is a pressing need for large-scale efforts at genome-wide perturbation followed by functional evaluation to identify causal variants and the contribution of these causal mechanisms to the pathogenesis of AD/ADRD. However, well-defined, scalable experimental approaches for functional interpretation of genetic variants are lacking. Emerging high-throughput sequencing-based assays and cellular assays have created the capability to perform comprehensive genomic measurements and functional readouts to dissect the function of genes and non-coding variants at the scale needed to follow up on the genetic association studies. A successful functional interpretation endeavor requires a multipronged approach that involves collaboration among scientists with expertise in genetics, genomics, and high-throughput screening technologies for large-scale, genome-wide investigation.
NIA has supported a robust program of research and infrastructure to study the genetics of AD/ADRD. To capitalize on the investment already made in the ADSP, this FOA supports a concerted effort, as an arm of the ADSP, aimed at filling the gaps in our understanding of genetic variants by moving from the discovery of disease-associated loci to elucidating functional consequences and disease mechanisms underpinning the genetic heterogeneity of AD/ADRD. Determining the functions of coding and non-coding genomic elements will improve genome annotation, increase understanding of disease endophenotypes, and ultimately facilitate the transition of genetic knowledge to the identification and prioritization of potential targets for novel diagnostics and therapeutics for AD/ADRD.
Through this FOA, NIA seeks to generate high-resolution, comprehensive maps of AD/ADRD-specific functional genomic elements and epigenomic signatures and characterize a broad range of functional elements, including ADSP-identified genes and loci and other AD/ADRD-specific non-coding variants, as well as non-coding RNAs. The goal of this FOA is to support concerted efforts that apply high-throughput genome-wide approaches to discover and characterize functional genomic and epigenomic elements and elucidate and validate their functional roles and mechanisms of action underpinning the heterogeneity, pathogenesis, and progression of AD/ADRD. Driven by the ADSP genetic discovery, studies funded under this FOA will take a multipronged, team-science approach that involves scientists with expertise in genetics, genomics, cell physiology, biochemistry, bioinformatics, and high-throughput screening technologies to develop cross-cutting activities and workflows to carry out large-scale functional studies.
A variety of experimental approaches may be taken. It is expected that projects funded under this FOA will apply comprehensive genome-wide approaches, computational methods, and high-throughput screening assays to systematically determine the biochemical and physiological functions of AD/ADRD-specific genes/loci and genetic variants and to comprehensively characterize the regulatory landscape modulated by non-coding variants and non-coding RNAs through genome-wide examination of human brain regions, cell types, and disease time course. Validation studies must be conducted on prioritized ADSP-identified genes and loci and other key functional genomic elements using in vitro, ex vivo, or in vivo systems.
It is expected that the awardees funded under this FOA will form the ADSP-Functional Genomics Consortium (ADSP-FGC) comprised of cross-linked, collaborative U01 applications with agreed-upon overarching goals and milestones. Each U01 application should have its own Program Director/Principal Investigator (PD/PI), and the program must provide a mechanism for cross-site coordination that is parallel to that of the ADSP.
The programmatic goals and funding priorities of the ADSP-FGC initiative are to ensure broad coverage of coding and non-coding genomic elements and to deliver high-resolution, comprehensive maps of functional elements. It is possible that multiple awardees may approach similar research questions, provided that their approaches and research emphasis are complementary.
Projects proposed by applicants to this FOA should build upon the efforts and resources currently supported by the ADSP consortium, as well as other related consortia such as PsychENCODE, the Genotype-Tissue Expression Project (GTEx), the Encyclopedia of DNA Elements (ENCODE), Common Fund Epigenomics, the Roadmap Epigenome Mapping Consortium (REMC), and the International Human Epigenome Consortium (IHEC).
Projects awarded under this FOA will be supported by existing NIA-funded infrastructure, including the Genome Center for Alzheimer’s Disease (GCAD), the NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS), and the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD). Investigators will collaborate with NCRAD, where resources related to this study can be obtained. Access to data generated by the ADSP-FGC will be provided through NIAGADS, which will act as a central hub for data storage and sharing. Investigators will coordinate efforts through NIAGADS to generate data that are consistent in presentation to the research community and to support the harmonization of data across the consortium and with other NIA-funded studies. Subcontracts to existing infrastructure grantees will be needed to support their efforts. Development of new infrastructure, such as databases, is not allowed. Investigators are encouraged to contact the Program Official for this FOA before submitting an application.
This FOA will support the development of robust high-throughput tools to ensure that large-scale, multi-modal functional data can be generated, analyzed, and interpreted in ways that are relevant to AD/ADRD pathophysiology to define causal mechanisms for the disease. This FOA will support the development of scalable functional assays, as well as disease-relevant cellular and tissue models, to aid mechanistic interpretation. Collectively as a research resource, the tools, reagents, and assays, along with the genomics data sets generated by the ADSP-FGC consortium, will be made rapidly available to the scientific community.
Proposed projects will focus on the discovery, elucidation, and validation of the biological functions and mechanisms of action of ADSP-identified genes and loci and a broad range of functional genomic and epigenomic elements and their roles involved in AD/ADRD risk or protection, pathogenesis, disease progression and severity, and outcomes relevant to AD endophenotypes and pathophysiological mechanisms. Applicants are encouraged to propose studies that will achieve a deeper understanding of cell-type-specific physiological functions and molecular mechanisms underlying the genetic heterogeneity of AD/ADRD. Applicants are especially encouraged to propose studies that will explore classes of functional elements that are currently understudied, such as non-coding variants and non-coding RNAs. Applications that are primarily oriented on computational analyses and/or modeling of existing data sets, with limited effort on experimental characterization and validation, are considered not responsive to this FOA.
Studies sought in this FOA include, but are not limited to, the following areas:
The ADSP-FGC awardees will participate in collaborative, synergistic research activities that could enrich the original project by leveraging the expertise and/or research developed by other awardees or consortia. The ADSP-FGC will also collaborate with other NIA-funded programs. The ADSP-FGC may serve as a bridge between the ADSP and Accelerating Medicines Partnership (AMP-AD) in order to accelerate the identification of therapeutic targets for specific AD/ADRD endophenotypes. The consortium will work synergistically with both the ADSP and AMP-AD in order to facilitate and accelerate scientific progress through the coordination of parallelized research strategies, analytical methods, and sharing of data and other research resources.See Section VIII. Other Information for award authorities and regulations.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
NIA intends to commit $5 million in FY 2021 to support up to 3 awards.
Direct costs should not exceed $1 million per year.
The maximum project period is five years
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Alison Yao, Ph.D.
National Institute on Aging (NIA)
Facilities and Other Resources and/or Equipment
Explain how the institutional environment(s) in which the ADSP-FGC project will operate will contribute to the probability of success in facilitating the AD research program it serves. As relevant, explain how the ADSP-FGC project will benefit from unique features of the institutional environment, infrastructure, or personnel? Describe any resources that are available within the scientific environment to support large-scale electronic information handling.
It is expected that key personnel will have adequate training, experience, and expertise in genetics, genomics, molecular biology, analysis of genome-wide data, or high-throughput experimental methodologies, as well as adequate expertise in computational and bioinformatics methodologies, biochemistry, cell physiology, and/or other fields relevant to the project. Key personnel should have a thorough understanding of the genetic and mechanistic complexity of Alzheimer’s disease and endophenotypes. They should have demonstrated experience and an ongoing record of accomplishments in effectively managing large, multidisciplinary research projects on genetics and/or functional genomics for complex diseases. They should demonstrate significant experience with coordinating collaborative (basic or clinical) research. Key personnel should have expertise in the handling and analysis of complex data sets, such as genetic, genomic, clinical, population substructure, and endophenotypic data related to complex diseases.The PD(s)/PI(s) and other personnel should have appropriate experience and training for management of large-scale data, with expertise in archiving, processing, and distributing phenotypic/endophenotypic data for AD. Key personnel with expertise in AD genomics and large-scale screening technologies and previous collaboration with ADSP investigators are critical to the success of the ADSP-FGC. Key personnel should have complementary and integrated expertise and skills. The PD(s)/PI(s) should have experience overseeing selection and management of sub awards.
All instructions in the SF424 (R&R) Application Guide must be followed.
Research Strategy: In addition to the strategy for achieving the scientific goals of the ADSP-FGC consortium, please address the following:
The following modifications also apply:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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 NIA Referral Office by email at firstname.lastname@example.org when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
How effectively will the project use high-throughput genome-wide approaches to expand our knowledge of the potential roles of various genomic and epigenomic elements implicated in the etiology of AD/ADRD? To what extent are the proposed plans sufficiently bold to establish a robust strategy to systematically characterize the functional genomic landscape of AD/ADRD and provide transformative insights and reveal novel mechanisms underlying the genetic heterogeneity of AD/ADRD? Is the proposed project needed to achieve the goals of the AD research programs it proposes to serve? How responsive and flexible is the proposed project, and is it likely to meet the evolving needs of the AD research community, including its ongoing collaborations and existing interactions with stakeholders? How likely is the proposed project to provide a means to better understand endophenotypes of AD/ADRD that may accelerate the discovery of therapeutic targets for AD/ADRD? Will coordinated receipt and distribution of genetic and genomic data facilitate or expedite AD research that would be delayed or infeasible if conducted as independent projects? How responsive is the proposed project to the need to serve as an interface between the ADSP and other consortia related to the genetics of AD?
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?
To what extent do the PD(s)/PI(s) and other key personnel have adequate expertise in genetics, genomics, computational and bioinformatics methodologies, molecular biology, biochemistry, cell physiology, analysis of genome-wide data, high-throughput experimental methodologies, and/or other fields relevant to the project, as well as expertise in and understanding of the mechanistic complexity of Alzheimer’s disease? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in effectively managing large multidisciplinary research projects on genetics and/or functional genomics for complex diseases? Do the investigators demonstrate significant experience with coordinating collaborative (basic or clinical) research? Do the investigators have complementary and integrated expertise and skills? Do the PD(s)/PI(s) have experience overseeing selection and management of sub awards, if needed? Do the PD(s)/PI(s) and other personnel have appropriate experience and training for management of large-scale data, with expertise in archiving, processing, and distributing phenotypic/endophenotypic data for AD? How facile are the PD(s)/PI(s) in curation of large data sets, including multiple layers of complex genomic data relevant to genetic analysis? How facile are the PD(s)/PI(s) in the understanding and management of functional genomics outcomes?
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?
Does the project propose genome-wide approaches for data generation, processing, integration, and multi-level analyses of diverse data types to characterize the biochemical, physiologic, and regulatory roles of functional genomic elements? Does the application propose novel organizational concepts in the field of AD functional genomics research or instrumentation in coordinating the AD research projects that the ADSP-FGC will serve? Are the proposed concepts, approaches, methodologies, instrumentation, or interventions novel to the field of AD research? Are the concepts, strategies, or instrumentation novel to AD genetics or genomics research or novelin a broad sense? Is a refinement, improvement, or new application of organizational concepts, data management strategies, or instrumentation proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the project? Are the leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the proposed project? Are potential problems, alternative strategies, and benchmarks for success presented that may impact AD research as a whole? Is an appropriate plan for workflow and a well-established timeline proposed? Does the application propose adequate and robust plans for experimental validation of functions and identification of underlying molecular mechanisms? Does the project adequately address issues of statistical power? Does the project adequately address the integration and collaboration with other projects of the ADSP-FGC and with other components of the ADSP Consortium including NIAGADS, NCRAD, and ADGC? Does the application utilize and/or develop robust and high-throughput genetic and epigenetic screening techniques and methods?
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?
Will the institutional environment(s) in which the ADSP-FGC project will operate contribute to the probability of success in facilitating the AD research program it serves? Will the ADSP-FGC project benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support large-scale electronic information handling?
For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
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:
Information regarding the disposition of applications is available 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.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
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.
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.
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 https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://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 https://www.hhs.gov/civil-rights/for-individuals/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.htmlor 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.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have primary responsibility for:
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:
For NIH staff, the designated NIA Project Scientist will have substantial scientific/programmatic involvement during conduct of this activity through technical assistance, advice, and coordination above and beyond normal program stewardship of grants, assisting in those aspects of the consortium described below. Project Officials (the NIA Project Scientist and Program Officer) will be ex-officio members of the committees that execute policy on behalf of the consortium. Awardees agree to accept the following assistance from the designated NIA Project Scientist:
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.
Areas of Joint Responsibility include:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
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 agreementsare 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.
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Alison Yao, Ph.D.
National Institute on Aging (NIA)
Marilyn Miller, Ph.D.
National Institute on Aging
Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
National Institute on Aging (NIA)
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