Required Application Instructions

It is critical that applicants follow the 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

The National Institute on Aging (NIA) requests submission of applications for a competition to continue and to extend the scope of the NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS).

NIAGADS was established in 2006 as a data storage site to act as a research resource for the NIA Alzheimer's Disease (AD) Genetics Initiative. NIAGADS archives, processes and distributes genetic data, and publicly displays results in accord with the Genomics of Alzheimer's Disease Sharing Policy. Data stored at NIAGADS include genetic, genomic, and phenotypic data relevant to genetic analysis such as clinical and neuropathology data elements, and related data provided by NIA funded investigators in keeping with the NIAGADS Data Distribution Agreement. Genetic, expression, epigenomic, and related data are available at the level of specific genes. Following a review process and approval by a Data Use Committee, NIAGADS makes available to qualified investigators several different types of data from genetic/genomic studies of late-onset Alzheimer’s disease (LOAD), including high-density genotyping and sequencing data; extensive phenotype data, and summary statistics from published genetic studies. The information technology employed serves to optimize the accessibility and usefulness of the information within the data base. Ongoing outreach efforts are designed to maximize data sharing in order to enhance research in AD. NIAGADS maintains an up-to-date listing of resources for researchers in the scientific community and has a flexible web-based data entry system using standardized common data elements for AD research studies that can be accessed by qualified investigators for a variety of basic science and clinical research studies.

The NIAGADS mission was broadened in 2012 when it was funded as a cooperative agreement simultaneous with the launch of the Alzheimer's Disease Sequencing Project (ADSP). ADSP genetic data are from large numbers of genetically informative, phenotypically well-characterized families having multiple individuals affected with AD, as well as from LOAD cases and controls. NIAGADS works in partnership with the Data Base for Genotypes and Phenotypes (dbGaP) on the ADSP effort, is fully engaged in providing infrastructure support for sequence data analysis, and participates in key ADSP Work Groups. NIAGADS acts as the data coordinating center for ADSP-related data including genome wide association studies (GWAS), whole genome sequence data (WGS), whole exome sequence data (WES), targeted genome sequencing data, phenotypic data and related primary and secondary analysis data. Applications for ADSP data are reviewed by the ADSP Data Access Committee (DAC) and the NIAGADS Data Use Committee. NIAGADS receives input on operations from an external board of consultants.

NIAGADS has the ability to accept and link to associated genetic and phenotypic data that are available in other AD-related databases, and has the capability to link with other genetic research resources such as the National Center for Biotechnology Information (NCBI) and related genomic databases. The research resource provides a large data storage site of publicly available sequence and annotation data along with an integrated tool set for examining and comparing the genomes of affected and unaffected individuals, aligning sequence to genomes, and displaying and sharing users own annotation data.

NIAGADS acts a key data repository for the ADSP, the Alzheimer Disease Genetic Consortium (ADGC),

the Consortium for Alzheimer's Sequence Analysis (CASA), and the network of NIA sponsored Alzheimer's Disease Centers (ADCs). Other ongoing collaborations include the National Alzheimer's Coordinating Center (NACC), the National Cell Repository for Alzheimer's Disease (NCRAD), the NHGRI funded Large Scale Sequencing and Analysis Centers (LSAC), dbGaP, the National Human Genome Research Institute (NHGRI) and other NIH Institutes and Centers (ICs). NIAGADS has developed working relationships with all of these entities. Future success depends on keeping the relationships together. Thus, an important aspect of NIAGADS' function is to continue to coordinate with dbGaP, NCRAD, and NACC and to provide infrastructural support for the ADGC, CASA, ADSP, and other NIA-funded genetic studies such as the ADSP Discovery Phase, the ADSP Replication Phase Analysis Studies, the Late Onset of Alzheimer's Disease (LOAD) Family Study, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), other multiple- and single-site studies that involve the collection and storage of data for genetic research on AD.

In the next five years NIAGADS should continue to work toward: 1]. Being a state-of-the-art genomics data repository that is enabled to store and provide to users genotypic, genomic, annotation, and epigenetic data as well as deep phenotype data for the various datasets it stores; 2]. Expanding the genomics database to enable users to perform novel analyses with existing data; 3]. Expanding the ability to annotate genomes, including especially annotation data for the ADSP by enhancing capabilities for annotation using tools such as Encyclopedia of DNA Elements (ENCODE); 4]. Identifying a suite of approaches that would allow the comprehensive identification of the functional elements in the human genome; 5]. Acting as a comprehensive resource to allow the scientific community to better understand how the Alzheimer's genome can affect risk for and protection against disease; 6]. Facilitating the discovery of genetic factors that may lead to the development of new therapies to prevent and treat the disease.

NIAGADS should continue providing overall ADSP project management of research and resource goals. The database should have the ability to receive and organize previously collected and new genetic, genomic, and phenotypic data. It should devise plans for working with a range of stakeholders including government, academic scientists, industry, and data-management experts including but not exclusive to NACC; NCRAD; the Alzheimer's Disease Neuroimaging Initiative (ADNI); the Accelerating Medicines Partnership (AMP) and AMP Sage Bionetworks (SAGE). The database should be enabled for cellular network/pathway analysis and visualization with the ability to interface with external databases to enable linking genetic/genomic data for rapid discovery of therapeutic approaches for AD.

The database should expand its user audience beyond AD geneticists/genomicists to geneticists/ genomicists for other complex neurological diseases, and should include genetic counsellors, clinicians, and neuroscientists in basic and clinical research as potential users by providing scientific expertise. This will require the skills and flexibility to apply cutting-edge science to the development and use of data analysis protocols and quality assurance/quality control measures. It will require coordination of the receipt, processing, storage, annotation, analysis and distribution of data from a variety of projects and the ability to link clinical data with various forms of genetic and genomic data. Projects supported by NIAGADS will include both academic and industry-based research. Data sharing, effective work flow management, and protocol standardization are expected to play a significant role in the success of these activities as an Alzheimer's community research resource. Community outreach and a user-friendly, query-based website are essential components of the overall activity of the database. NIAGADS will distribute data to qualified investigators for use in research studies following government guidelines and regulations.

It is expected in the next five-year funding period that NIAGADS will expand its scope to ensure that the NIAGADS will have a central data repository that will meet the needs of genetic/genomic research on AD and related neurodegenerative diseases, with an emphasis on deep endophenotypes. NIAGADS should be a state-of-the-art central data repository for data (genetic, genomic, annotation, analysis, statistical and phenotypic) collected by other NIA-funded studies with the capability to work in the cloud environment.

In 2016, NIA intends to fund an NIA Coordinating Center for the Genetics and Genomics of Alzheimer's Disease (U54) to facilitate and support the analysis and harmonization of the next phase of the ADSP activities. The NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease will serve as a focal point for the next phase of the ADSP that will include joint ADSP data analysis, harmonization, and sharing. NIAGADS will act as an interface between the ADSP, the AD research community, and the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease.

In summary, this FOA addresses NIA's vital need for a central database for the storage and exchange of AD genetics and related data. The NIA is committed to facilitating the collection and sharing of data related to research in the area of the genetics of AD. NIAGADS is a critical facet of the NIA Alzheimer's Disease Genetics Initiative that effectively leverages the investments already made related to the etiology of AD. Applications considered for funding should effectively leverage the investments already made related to investigation of the root causes of the disease. The research resource should provide a large database of publicly available sequence and annotation data along with an integrated tool set for examining and comparing the genomes of affected and unaffected individuals, aligning sequence to genomes, and displaying and sharing users own annotation data. Besides data storage and data processing, the database should provide effective mechanisms for data distribution.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not 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).

Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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:

Marilyn Miller, Ph.D.
National Institute on Aging
Telephone: 301-496-9350
Fax: 301-496-1494
Email: millerm@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. It is expected that PD(s)/PI(s) and other personnel will have appropriate experience and training for management of large scale data bases with expertise in archiving, processing and distributing genetic data, and publicly displaying data. The PD/PI should be facile in curation of large datasets, including genetic, genomic, and phenotypic data relevant to genetic analysis such as clinical and neuropathology data elements, and related data provided by NIA funded investigators. The PD/PI should have demonstrated experience and an ongoing record of accomplishments in effectively managing a database in order to discover risk and protective genetics factors for AD. The PD/PI should demonstrate significant experience with coordinating collaborative [basic or clinical] research. If the application is multi-PD/PI, investigators should have complementary and integrated expertise and skills in order to provide appropriate leadership approach, governance, plans for conflict resolution, and organizational structure applicable to the database. The applicant should have experience overseeing selection and management of sub awards, if needed.

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

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

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

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

Specific Aims: Provide a succinct description of how the proposed work will meet or continue to meet the overall scientific goals, the expected outcomes, and the impact of NIAGADS, should those goals be achieved. Refer to the Funding Opportunity Description in Section I when formulating specific aims.

Research Strategy: Provide an overall description of the proposed organizational structure and project management plan and show how it will serve particular communities of researchers studying Alzheimer's disease.

Describe the strategy for effectively carrying out each specific aim including the establishment of an Executive Committee comprised of lead investigators from major AD genetics studies. Applicants should present an integrated plan that will be responsive and flexible regarding the evolving needs of the scientific community especially the Alzheimer's Disease Sequencing Project and other major AD genetics projects.

Show how the plan to arrange coordinated receipt, storage, annotation, analysis, and distribution of genetic and genomic data will facilitate research in Alzheimer's disease that is supported in independent projects. Refer to the funding Opportunity Description in Section I when developing the Research Strategy.

Innovation: Explain how the concepts, approaches or methodologies, instrumentation, or interventions used in the development of the database are novel to the field of AD research. Explain how refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed are novel to the field of AD research. Explain any novel organizational concepts, management strategies, or instrumentation in coordinating the research projects that the database will serve. Describe any concepts, strategies, or instrumentation that are novel to the genetics and genomics of AD research or that are applicable in a broad sense. Explain any refinement, improvement, or new application of organizational concepts, management strategies or instrumentation that will be employed in the research.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan that is consistent with the NIA Genomics of Alzheimer's Disease Sharing Policy and the goals of the NIA Genetics of Alzheimer's Disease program. It is the policy of the NIA that all Genomic Data derived from NIA funded studies for the genomics of late onset Alzheimer’s disease, including secondary analysis data, be deposited at NIAGADS or another NIA approved site or both whenever possible. As a resource, more information can be found at: https://www.nia.nih.gov/research/dn/alzheimers-disease-genomics-sharing-plan

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

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

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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials 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? Is the proposed Data Storage Site needed to achieve the goals of the Alzheimer's disease (AD) research programs it proposes to serve? How responsive and flexible is the proposed Data Storage Site likely to be to evolving needs in the AD research community including its ongoing collaborations and existing interactions with stakeholders? 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? What advantages will the repository bring to the AD research programs it services? How responsive is the proposed database to the need to serve as an interface between the ADSP, the AD research community, and the NIA Coordinating Center for the Genetics and Genomics of Alzheimer's Disease?

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? Are the PD(s)/PI(s) and other personnel well suited to their roles in the Data Storage Site? Do the PI(s)/PI(s) have experience in handling AD genetics, genomics, and phenotype data? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in effectively managing the database in order to discover risk and protective genetic factors 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? Are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the AD genetics and genomics database? 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 bases with expertise in archiving, processing and distributing genetic data for AD, and publicly displaying data? Is the PD/PI facile in curation of large datasets, including genetic, genomic, and phenotypic data relevant to genetic analysis such as clinical and neuropathology data elements, and related data? Does the PD/PI have experience and an ongoing record of accomplishments in effectively managing a database in order to discover risk and protective genetics factors for AD? Do the PD(s)/PI(s) provide a plan to form an executive committee that oversees the work and that ensures that the AD community is well served by the genetics and genomics database? If the application is multi-PD/PI, do investigators have complementary and integrated expertise and skills in order to provide appropriate leadership approach, governance, plans for conflict resolution, and organizational structure to the AD genetics and genomics database?

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 application propose novel organizational concepts in the field of AD genetics or genomics, management strategies, or instrumentation in coordinating the AD research projects that the database 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 applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, 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 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? Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the projects that the AD database will serve? Are potential problems, alternative strategies, and benchmarks for success presented that may impact AD research? Does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the projects as related to the AD research community? Are an appropriate plan for work-flow and a well-established timeline proposed?

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?

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 in which the Data Storage Site will operate contribute to the probability of success in facilitating the AD research program it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the infrastructure proposed? Will the database benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Not Applicable

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:

• Will receive a written critique.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . 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.

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 as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The PD/PI(s) will have primary authorities and responsibilities to define objectives, approaches, and analysis protocols; data analyses and interpretation; follow-up analysis; and quality control. The PD/PI(s) will work directly with members of the NIA Alzheimer's Disease Genetics Consortium (ADGC), the National Alzheimer's Coordinating Center (NACC), the National Cell Repository for Alzheimer's Disease (NCRAD), the Alzheimer's Disease Centers (ADCs), Alzheimer's Disease Genetics Consortium (ADGC), the Consortium for Alzheimer's Sequence Analysis (CASA), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Alzheimer's Disease Sequencing Project (ADSP), NHGRI, NIA, the ADSP Discovery Phase cooperative agreement studies funded under https://grants.nih.gov/grants/guide/pa-files/PAR-12-183.html the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease (U54) - https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-16-001.html#sthash.CkRnSTCU.dpuf and the Alzheimer's Disease Sequencing Project (ADSP) Replication Phase Analysis Studies (U01): https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-16-002.html#sthash.DDPm7mTO.dpuf and other NIA funded investigators.

The NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) Program Director(s) in consultation with the NIA Project Scientist will establish a board of external consultants to provide guidance on analytical methods and advances in methodology appropriate for use in this context. Consultants will be selected as individuals who are not involved in AD genetics research but who could advise the awardees with an emphasis on analytical methods.

The PD/PI(s) and key NIAGADS personnel and selected awardees of the Alzheimer's Disease Sequencing Project (ADSP) Discovery Phase and Replication Phase, in consultation with the NIA Project Scientist, will form an Executive Committee. The Executive Committee will hold meetings and conference calls to facilitate development and implementation of common measures and practices. The Executive Committee will define the rules regarding access to, and publication of, findings from analyses of common data. NIA-funded study sites will transfer genetic data to the Data Storage Site.

A Data Use Committee, selected by the NIA Project Scientist in collaboration with the awardees of the cooperative agreement, will be formed which will act in a decision making capacity for use of the data that are stored at the Data Storage Site, for data that are provided to the Data Storage Site, and for review of ADSP applications in concert with the ADSP Data Access Committee. Institutions providing data will retain custody of, and primary rights to, the site-specific data developed under their individual awards, in keeping with Institutional Review Board approval, and subject to Government rights of access, consistent with current HHS, PHS, and NIH policies.

The Program Director of the Data Storage Site will work collaboratively with other investigators to develop the study analysis design, collect appropriate data, and perform analyses for the AD genetics community as approved by the Executive Committee in consultation with the NIA Project Scientist. .

The PD/PI(s) of the cooperative agreement will be involved in collaborations with the Alzheimer's Disease Genetics Consortium (ADGC, http://alois.med.upenn.edu/adgc/), the Consortium for Alzheimer's Sequence Analysis (CASA), the Alzheimer's Disease Centers (ADC, http://www.nia.nih.gov/Alzheimers/ResearchInformation/ResearchCenters/), the National Cell Repository on Alzheimer's Disease (NCRAD http://ncrad.iu.edu/), and the National Alzheimer's Coordinating Center (NACC http://www.alz.washington.edu/), and the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease (CGAD) during all phases of the award. The PD/PI(s) of the cooperative agreement will administer the establishment, operation, and quality control of genotypic and phenotypic data, including the development of procedures for assuring data quality control, and procedures for transfer of data generated by NIH funded investigators into the database. The PD/PI(s) of the cooperative agreement is responsible for working cooperatively with study sites and sponsoring organizations and for overseeing the implementation of, and adherence to, common protocols, as well as assuring quality control of the data collected. In addition to organizing and attending regular meetings, the PD/PI(s) of the cooperative agreement will be expected to maintain close communications with the NIA Project Scientist and, where appropriate, the Program Directors of the ADSP and the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease. The PD/PI(s) will ensure that ADSP data are made available immediately upon deposition into the Data Storage Site. The NIA Project Scientist will have substantial scientific involvement that is above and beyond the normal stewardship role in awards, as described below.

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

The NIA Program Official will be responsible for normal program stewardship including assessing the progress toward the accomplishment of specified milestones, and for recommending release of additional funds to the project. The designated NIA Project Scientist will have scientific involvement during conduct of this activity, through technical assistance, advice and coordination, assisting in those aspects of the award as described below. The NIA Project Scientist will monitor the deposition of data into the Data Storage Site to ensure that NIA funded investigators have appropriately deposited data and have properly acknowledged the use of the Data Storage Site in the publication of their work. The NIA Project Scientist will review protocols for work flow and data sharing before they can be implemented. The NIA Project Scientist will be a non-voting "ex officio" member of the Executive Committee and all key subcommittees.

Areas of Joint Responsibility include:

For areas of joint responsibility, an Executive Committee including Program Director(s) of the Data Storage Site, selected Program Director(s) from the ADSP, the NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease, and the NIA Project Scientist should be formed. The Executive Committee will serve as the main decision-making body for the shared aspects of the study and will devise common protocols related to data sharing among collaborators, stakeholders, and the AD research community. Appropriate Data Storage Site staff may attend the Executive Committee Meetings as needed. Members of the Executive Committee for the Data Storage Site will contribute to the effort by accessing and assessing appropriate genetic and phenotype data, and providing expertise in the analysis of genetics data from specific AD cohorts. The Executive Committee will meet bi-monthly, or as needed.

The external board of consultants will advise the PD/PI(s) on analytical approaches; phases of the award will proceed only after review of the common protocols and approval by the Executive Committee, and acceptance by the NIA.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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 progress report, 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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

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

Marilyn Miller, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: millerm@mail.nih.gov

Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9666
Email: Vemuri@nia.nih.gov

Robin Laney
National Institute on Aging (NIA)
Telephone: 301-496-1473
Email: laneyr@mail.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.