Part 1. Overview Information

Key Dates

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

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

The National Institute on Aging (NIA) invites applications for the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD). NCRAD was established in 1990 to recruit, collect, maintain, and distribute information and biological specimens on large numbers of genetically informative, phenotypically well-characterized families having multiple individuals affected with Alzheimer's disease (AD). Initial efforts were focused on the recruitment of early onset, autosomal dominant families. Subsequently, NCRAD expanded its focus to include late onset families as well as kindreds with familial non-AD dementia, such as the fronto-temporal disorders.

In 2003, NCRAD became the repository for a large NIA-sponsored genetics initiative to expand the collection of families with late onset AD (Late Onset Alzheimer's Disease (LOAD) Family Study). In addition, NCRAD has become a key repository for the NIA-sponsored Alzheimer's Disease Centers, the Alzheimer Disease Genetic Consortium (ADGC), and the Alzheimer's Disease Sequencing Project (ADSP), which have led collaborative efforts among U.S. dementia researchers.. An important aspect of NCRAD’s function is the continued coordination with the National Alzheimer’s Coordinating Center (NACC) and infrastructural support for the ADGC, ADSP, and other NIA-funded studies such as the LOAD Family Study, Alzheimer's Disease Neuroimaging Initiative (ADNI), and other multiple- and single-site studies that involve the collection and banking of biospecimens for research on Alzheimer's disease and other dementias.

In 2018, NIA supported the expansion of the number of studies and types of samples NCRAD collected to address increasing needs in the AD research community. Additionally, NCRAD supports multiple new NIA-funded national efforts (including ABC-DS and the Alzheimer’s Gut Microbiome Project) and should plan for continued increases in capacity to support future studies.?Major goals for the next period will be to continue to diversify collected samples, both in terms of participant demographics and types of studies, and increase the availability of samples through active promotion that assures their maximum utility by a wider research community.

In the next 5 years NCRAD will continue to:

• Maintain, enhance, and expand the existing NCRAD infrastructure to continue to provide a centralized resource and repository for DNA, cell lines, plasma, serum, RNA, brain tissue, cerebrospinal fluid and peripheral blood mononuclear cells or fibroblasts, induced pluripotent stem cells (IPSCs), and other emerging biological samples and reagents.
• Provide overall biorepository management expertise, including procedure manual development, training videos, site training, sample kits, direct study support (calls and meetings), data reconciliation (as needed), and the ability to receive and track previously collected biosamples and new biospecimen collections. Applicants should include plans for working with a range of stakeholders, including government, academic scientists, industry, and large national projects, such as NACC and NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS).
• Support projects by supplying needed scientific and laboratory expertise. Apply cutting-edge science to the development and use of biospecimen protocols and QA/QC assays. Coordinate the receipt, processing, storage, and distribution of biospecimens from a variety of projects, and support the review and recommendation by NCRAD Biospecimen Review Committee (BRC) for approval by NIA.
• Assure linkages connecting clinical data with biosamples. Projects supported by NCRAD will include both academic and industry-based research. Data sharing and protocol standardization is expected to play a significant role in the success of this as a community research resource.
• Maintain a user-friendly, query-based website as an essential component of the overall activity. Provide dynamic bidirectional interactions/links with other resources such as NACC and NIAGADS to ensure the connection of biological samples, clinical information, and data generated from the samples. Support a tracking system to monitor, collect, and report usage statistics regarding information requests, sample and data distribution, and website visits.
• Continue to provide, in consultation with NIA, terms and conditions of the Material Transfer Agreement (MTA) for biosample deposition in NCRAD that assures data are returned and made available to other researchers. Develop a Standard Operating Procedure (SOP) to provide investigators with instructions to initiate and complete the MTA.

In the next five-year funding period, it is expected that NCRAD will continue to expand to meet the growing needs of a wide variety of research on Alzheimer's disease and related neurodegenerative diseases, such as Frontotemporal Degeneration, Lewy Body disorders, and Down Syndrome. NCRAD should be a state-of-the-art central biospecimen repository for samples (DNA, cell lines, plasma, serum, RNA, brain tissue, stool, fibroblasts, peripheral blood mononuclear cells, iPSCs) collected by other NIA-funded studies. NCRAD will distribute data and biospecimens to qualified investigators for use in research studies following government guidelines and regulations.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Only the U24 awardee currently supported through PAR-15-316 is eligible to submit a renewal (Type 2) application via this funding opportunity.

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 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) 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 to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guideexcept 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. 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.

Other Attachments:

• Highlight the organization's procedures. Please name your file "Standard Operating Procedures.pdf".
• Describe what samples are available and how collaborators will access the samples. Please name your file "Catalogs.pdf".
• Provide a master list of acronyms. Please name your file "Acronym_Dictionary.pdf".
• Describe a plan for raising awareness of this resource to maximize its use in the scientific community. Please name your file Dissemination.pdf .

The filename provided for each Other Attachment will be the name used for the bookmark in the electronic application in eRA Commons.

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

Specific Aims: Provide a succinct description of how the proposed work will meet the overall scientific goals, the expected outcomes, and the impact of NCRAD, 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. Provide an explicit strategy for assuring that the samples included in the repository reflect an increase in the diversity of the research participants from whom they are collected.

Describe the strategy for effectively carrying out each specific aim, including the plan and process for an Executive Committee. Applicants should present an integrated plan that will be responsive to and flexible regarding the evolving needs of the scientific community.

Show how the plan to arrange coordinated receipt and distribution of biospecimens will facilitate research in Alzheimer's disease and related dementias that is supported by independent projects. Refer to the funding Opportunity Description in Section I when developing the Research Strategy.

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

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• All Standard Operating Procedures, laboratory manuals, and other procedural documents are expected to be made freely available, in order to allow harmonization across studies and in order to have full transparency regarding laboratory procedures, thus limiting the risk of batch effect in biomarkers research findings.

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

Applicants must include the following items in the Appendix:

• Laboratory Protocols including QA/QC activities and sample aliquoting procedures
• Screenshots of database views if relevant to data management capabilities
• Standard operating procedures for equipment monitoring and maintenance
• Facility-derived training, continuing education, and certification programs for personnel

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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.

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

Section V. Application Review Information

1. Criteria

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

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.

Significance

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?

Is the proposed repository needed to achieve the goals of the research programs it proposes to serve? How responsive is the proposed structure likely to be to evolving needs in the community, including the Alzheimer’s Disease Genetics Consortium, the Alzheimer’s Disease Sequencing Project, and other major genetics projects? Will coordinated receipt and distribution of biospecimens facilitate or expedite research that would be delayed or infeasible if conducted as independent projects? What advantages will the repository bring to the research programs it services?

Investigator(s)

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

Innovation

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

Approach

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?

Environment

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

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

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

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute on Aging, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA. Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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.

2. Administrative and National Policy Requirements

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

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 the primary responsibility for:

• The awardee, as National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) PD/PI, will coordinate project activities scientifically and administratively at the awardee institution and will have primary responsibility for performing all scientific and fee-for-service activities. The PI agrees to accept the close coordination, cooperation, and participation of the NIA Scientific Officer and NCRAD Executive Committee (NEC) in those aspects of scientific and technical management of the project as described below.
• Specifically, the PD/PI will:
• Develop guidelines and procedures related to NCRAD operations and seek approval from the NEC.
• Design protocols, oversee the provision of services and research resources to the scientific community, and work cooperatively to set project milestones, in consultation with NIA program staff and the NEC.
• Receive biomaterials and data files from the Alzheimer's Disease Centers (ADCs), the National Alzheimer's Coordinating Center (NACC), and other scientists; ascertain that proper informed consent exists for all samples; develop a unique coding system for each sample that de-identifies patient data; and distribute biomaterials and data files to qualified researchers granted access by criteria set up by the NEC and consistent with NIH data and biomaterials sharing policies (see below).
• Provide free DNA extraction and banking for all NIA-funded ADCs and other dementia-related studies approved by the NEC.
• Define a protocol detailing the requirements for sharing of genotypic data to a central data bank from scientists using cells and DNA obtained from NCRAD.
• Maintain a log of NCRAD usage that records the products and services provided and the fees charged.
• For each non-competing renewal, submit progress reports in the standard format, as required by NIH. The progress report will describe the activities and accomplishments of the NCRAD for the preceding award period and the goals to be accomplished during the renewal period. The progress report will include the log of NCRAD usage. The contents of the progress report will be used by the NIA program officer, along with other information, to determine the amount of funding the Cell Bank will receive for the renewal period.
• Organize and set the agenda for at least one meeting of the NEC, with additional advisors as appropriate, each year, along with teleconferences as needed. The awardee will have one vote on the NEC and will accept any modification, deletion, or addition of NCRAD activities approved by the NEC. The PI will be responsible for preparing, within 30 days, a concise summary of each NEC meeting or teleconference for distribution to participants.
• Attend and participate in ADC Directors' twice-yearly meetings

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

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

The NIA Project Scientist will have substantial scientific involvement during the conduct of this activity through technical assistance, advice, and coordination above and beyond normal stewardship. This includes facilitating the partnership relationship between the NIA and the NCRAD, helping to maintain the overall scientific balance in the program commensurate with emerging research opportunities, and ensuring that the activities of the Cell Bank are consistent with the scientific mission of the NIA Alzheimer's Disease Genetic Initiative. Access to research resources maintained in the Cell Bank will be determined by the NEC with input from NIA and consistent with NIH sharing policies (see below). The NIA Project Scientist shall be a voting member of the NEC. The Program Official (see below) and other NIA staff involved with the genetics initiative may also attend meetings of the NEC as observers but will not have voting privileges.

Specifically, the NIA Project Scientist will:

• Provide relevant scientific expertise and overall knowledge.
• Advise the NCRAD Director regarding recruitment of members and replacement of existing members of the NEC, should any choose to leave.
• Attend NEC meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Participate with other NEC members in the group process of setting priorities and milestones, deciding optimal approaches and protocol designs, and contributing to the adjustment of protocols or approaches as warranted.
• Serve as administrative liaison to NACC and the ADCs and help coordinate NCRAD activities with those complimentary programs. The NIA Project Scientist will coordinate NCRAD activities with the scientific mission and evolving goals of the NIA Alzheimer's Genetics Initiative, with input as required from the NEC and other NIA staff. The NIA Project Scientist will also coordinate NCRAD activities with other US and international efforts that focus on sharing research resources for genetic analyses of complex diseases.

The NIA Program Official is responsible for normal stewardship of the Cooperative agreement and will:

• Serve as program liaison between the NCRAD and other NIA staff involved in the Genetics Initiative.
• Assist in promoting and encouraging the sharing of unique research resources for genetic studies of Alzheimer's disease and other dementias of aging by the scientific community at large.
• Retain the option to recommend re-allocating NIA support provided to the NCRAD as scientific goals evolve.
• Determine the amount of support that will be awarded to the NCRAD as a non-competing renewal. The progress report received from the Cell Bank, along with other information, will be used to make this determination. The criteria used for this decision will include, but not be limited to, NCRAD productivity, e.g.. number of samples banked and distributed, customer satisfaction, and successful performance of the NCRAD in providing services to the genetic research community.

Scientific Oversight - NCRAD Executive Committee (NEC):

The NEC will meet at least once each year and will oversee NCRAD activities to assure that the needs of the broader scientific community for research resources necessary for the genetic analysis of Alzheimer's disease and other dementias of aging are being met. NEC will provide oversight of the Cell Bank and scientific advice to NIA. NEC members will provide scientific and operational oversight concerning both long-term developments and distribution activities at NCRAD. NEC also will consult on the incorporation of emerging genomic and genetic tools and technologies into NCRAD activities.

The NEC will consist of approximately 10 scientists,including the Director of NACC and the NIA Project Scientist. NEC members will be selected by the NCRAD Director after consultation with NIA. Members will be selected for their broad expertise in relevant topics such as molecular biology, molecular genetics, genomics, pharmacogenomics, statistical genetics, epidemiology, bioinformatics, cell and DNA banking, and Alzheimer's genetics. One member of the NEC will be appointed by the NCRAD Director/PI to chair the NEC after consulting with NEC members and NIA.

Additional NEC members may be added with agreement between the NEC and NIA. The NIA Project Scientist (voting member) and Program Official (non-voting member) will attend NEC meetings and will act as representatives of NIA. Other NIA staff involved with the Genetics Initiative may attend NEC meetings to help facilitate specific discussions. The NIA Program Official will consider NEC opinions with regard to overall NCRAD functioning and when making determinations for renewal funding.

Data Sharing:

Providing access to data and biomaterials collected in Alzheimer's genetic studies for qualified investigators in the wider scientific community is a guiding principle of the NIA Alzheimer's Genetics Initiative. To address the joint interests of the government in the availability of, and access to, the results of publicly funded research and in the opportunity for economic development based on these results, NIA expects that the information to be shared will include clinical, diagnostic, and pedigree structure information, in addition to cell lines and DNA. Oversight for this process will be provided by the NEC and NIA.

More specifically, it is expected that NCRAD will, when requested: (1) establish cell lines, from which DNA will be extracted and stored; (2) provide data to qualified investigators related to the clinical phenotype, diagnostic criteria, and pedigree structure for cell lines, DNA, and other specimens from the NCRAD; and (3) set up mechanisms by which data and biomaterials can be made easily available to qualified investigators in the scientific community

Areas of Joint Responsibility include:

None. All responsibilities are divided between awardees and NIH staff as described above.

Dispute Resolution:

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative 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.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission by the due date, and post-submission issues)

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

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

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

Cerise Elliott, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: elliottce@mail.nih.gov

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

Jennifer Edwards
National Institute on Aging (NIA)
Telephone: 301-827-6689
Email: edwardsj@mail.nih.gov

Section VIII. Other Information

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