NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a landmark, public-private partnership that has made major contributions to our understanding of Alzheimer’s Disease and to the ability of industry and non-industry sponsors to carry out registration trials of disease modifying interventions. ADNI has also been a pioneer in scientific transparency and data-sharing: putting all of its (de-identified) data online and available to all qualified investigators.

ADNI began October, 2004, as a cooperative agreement between the National Institute on Aging (NIA) and the Northern California Institute for Research and Education (NCIRE) to develop a multi-site, longitudinal, prospective, naturalistic study of normal cognitive aging, mild cognitive impairment (MCI), and early Alzheimer's disease (AD) as a public domain research resource . Substantial additional support was provided by a consortium of 21 industry and foundation partners through the Foundation for NIH (FNIH).

ADNI subjects were followed longitudinally with repeated clinical and neuropsychological evaluations, MRI imaging, FDG-PET scans, and plasma and CSF biomarkers. During the initial 5 year support period, revisions to the project added Genetics and Neuropathology Cores, and PiB PET imaging in a subset of sites. The American Recovery and Reinvestment Act (ARRA) of 2009 funded ADNI-GO, expanding the cohort to include milder MCI subjects and adding PET amyloid imaging at all sites. In 2010, NCIRE submitted a competitive renewal application for the cooperative agreement, extending follow-up, replacing dropouts, and focusing on earlier detection. ADNI2 was funded by NIA and the FNIH consortium of private partners in 2011. A cohort of subjects with subjective memory complaints but normal testing was also added. A competitive revision to pilot tau PET imaging was awarded in early 2015. ADNI2 is currently funded through July 2016.

ADNI1, ADNI-GO, and ADNI2 are natural history studies in a cohort representative of subjects who participate in AD randomized clinical trials (RCTs). ADNI2 involves 55 clinical sites across the United States and Canada, and follows more than 1000 subjects: ranging from healthy, elderly controls with normal cognition, to cognitively and functionally impaired patients with early AD, as well as patients with intermediate levels of impairment or subjective memory complaints. The FNIH consortium of private partners now includes 32 members.

ADNI’s major accomplishments include:

• Validating biomarkers to be used in selecting subjects for interventional RCTs during the earliest stages of AD: demonstrating changes in CSF -amyloid 42 and tau, and amyloid PET, that presumably reflect initial steps in AD pathology in mildly symptomatic, and even some asymptomatic subjects.
• Standardizing methods for magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers, enabling multicenter AD studies. ADNI methods have become a standard for industry and academia.
• Demonstrating the feasibility and value of multicenter PET amyloid imaging.
• Demonstrating that a significant portion of healthy, elderly controls have beta amyloid in their brains, and may be at increased risk for cognitive decline and AD.
• Demonstrating that decreased hippocampal volume on MRI is associated with disease progression.
• Creating an online database and sharing de-identified study data with almost 2,500 non-ADNI investigators, who have used the data to publish more than 350 papers
• Fostering the establishment of ADNI-like programs in many other countries, leading to worldwide collaborations between academic, government and industry investigators.

• Understand and characterize clinical AD pathobiology
• Identify biomarkers to detect AD at its earliest stages
• Identify biomarkers associated with disease progression, including potential surrogate endpoints.
• Work in a precompetitive space to develop biomarkers to facilitate multicenter RCTs of disease modifying interventions for AD
• Share de-identified clinical and biomarker data as they are gathered, without embargo

ADNI helped establish the value of PET amyloid imaging in a precompetitive, research use only setting. Subsequent to this, PET amyloid radio-tracers from three different industry sponsors (Avid/Lilly - Amyvid, Piramal Neuraceq, and GE Vizamyl) were approved by the Food and Drug Administration (FDA) and are now commercially available in the US. While ADNI had an important role in establishing the scientific and clinical utility of PET amyloid imaging, it had no role in the regulatory approval of any particular radio-tracer. It is essential for ADNI to continue working in the precompetitive space, where transparency, data sharing, and unfettered access to results have paramount importance. Industry support remains crucial for ADNI, but this collaboration, and ADNI’s work must take place in the public domain.

In recent years, PET tau imaging radio-tracers have been developed by groups in industry and academia. Tau PET imaging is only beginning to be applied in clinical settings (ADNI2 has initiated a tau PET pilot). Preliminary results appear promising: but remain, preliminary. One goal for ADNI3 should be to explore the role of tau PET imaging in clinical AD research. Baseline and longitudinal tau PET imaging in the ADNI cohort of healthy controls, subjects with MCI, and AD, combined with correlation to clinical outcomes and changes in other biomarkers can establish the value of this new biomarker.

ADNI is a unique, shared scientific endeavor. It has not been, and should not be devoted to testing any particular hypothesis about AD, but should provide the clinical data and biosamples needed by academic and industry investigators to generate and test models of AD onset and progression. The project, by itself, will not conquer AD, but ADNI will provide the scientific ammunition needed by the field to understand the pathobiology of AD and to find a disease modifying intervention.

ADNI has 9 different Cores, whose functions should continue to be provided in any renewal. Their duties include:

• Administrative Core: leads and coordinates the entire project
• Clinical Core: collects clinical data, interfaces with and monitors the clinical sites; curates clinical data before transfer to Informatics Core
• MRI Core: oversees collection of anatomical and functional MRI data by clinical sites; establishes scanning protocols; ensures data quality; manages and curates MRI data before transfer to Informatics Core
• PET Core: oversees collection of PET data (FDG, amyloid, tau, and any other tracers) by clinical sites; establishes scanning protocols, ensures data quality; manages and curates PET data before transfer to Informatics Core
• Biomarker Core: collects, stores, and curates CSF and blood samples collected by clinical sites; transfers samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to use ADNI biosamples; performs standardized assays for specific analytes in CSF and/or plasma from all subjects and transfers data to Informatics Core
• Genetics Core: collects, stores, and curates genetic materials collected by clinical sites; transfers samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to use ADNI genetic materials; performs specific standardized genetic analyses on all subjects and transfers data to Informatics Core
• Neuropathology: collects, stores, and curates the ADNI brain bank; coordinates post-mortem collection of brains by clinical sites; transfers brain samples to investigators approved by an independent Resource Allocation Review Committee (RARC) to study ADNI brain materials; provides standardized post-mortem neuropathological evaluations and transfers data to Informatics Core
• Biostatistics: provides biostatistical consultation and support to other Cores and to ADNI, overall
• Informatics: maintains the ADNI database; manages and shares ADNI data with qualified investigators, maintaining subject anonymity and ensuring data integrity

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.

Eligibility is limited to applications from organizations previously funded through the prior ADNI FOA, RFA-AG-04-005.

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) (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.

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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 can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Core	6

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of one
• Cores: required; maximum of ten

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Address the overall aims of ADNI.

Research Strategy

Significance: Focusing on ADNI as a whole, address (i) the importance of the problem or critical barrier to the field that ADNI addresses, (ii) how ADNI will improve scientific knowledge, technical capability, and/or clinical practice in one or more broad fields, (iii) how the concepts, methods, technologies, treatments, services, or preventive interventions that drive this field will be changed if the proposed aims are achieved.

Innovation: Considering ADNI as a whole, show how the proposed research seeks to shift current research or clinical practice paradigms through use of novel concepts, approaches, methodologies, instrumentation, or interventions. Demonstrate that these concepts, approaches, methodologies, instrumentation or interventions are novel to the research field or novel in a broad sense. Demonstrate that the proposed work refines, or improves, or applies in a new way, the concepts, approaches, methodologies, instrumentation or interventions proposed.

Approach: Include the major approaches and studies involved in the application showing how the approaches of different cores complement each other or are interdependent to allow the contribution of ADNI to be greater than the total of the individual contributions of the cores. Describe the mechanisms that will ensure the coherence of the project and maintain a multidisciplinary focus. Identify and justify any substantive changes in approaches from the prior period

Progress Report: Report on progress since the previous renewal

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.

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.

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: The Administrative Core provides overall leadership to ADNI and the aims should show the elements by which leadership and integration will be achieved

Research Strategy:

Significance: Describe how the activities of the administrative core will implement the overall vision of ADNI as an integrated investigation

Approach: Describe how the several elements proposed in the administrative core will be operationalized to achieve transparent communication and collaboration across projects and cores. Elements should include, but not be limited to, means for internal quality control of research; management of day-to-day program activities, management of contractual agreements, resolution of disputes, and allocation of funds.

Innovation: This section is optional

Progress Report: Report on progress since the previous renewal.

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.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. Information for all Cores should be submitted in the Administrative Core.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. Information for all Cores should be submitted in the Administrative Core.

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Core
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Core)

In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.

Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Core)

Specific Aims: Describe the overall role the core will play in ADNI

Research Strategy: Significance: Describe how the activities of the core will contribute to the overall goals of ADNI

Approach: Describe how the Core will carry out its functions and how it will interact with other Cores.

Innovation: This section is optional

Progress Report: Report on progress since the previous renewal.

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.

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.

Planned Enrollment Report (Core)

Not Applicable

PHS 398 Cumulative Inclusion Enrollment Report (Core)

Not Applicable

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. 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.

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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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.

Important reminders:

All PD(s)/PI(s) and component Project Leads 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.

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 (SAM). 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 NIA, 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 NOT-OD-13-030.

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? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

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

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.

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 .

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

Reviewers will provide a critique and an impact score of each core to reflect their assessment of the likelihood and extent to which the core will contribute to ADNI's ability 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 proposed Core).

Reviewers will consider each of the review criteria below in determining how the core contributes to the merit of the application as a whole. As cores are generally resources to enable or to advance research, Innovation is not considered routinely as an independent review criterion for cores. Innovative cores may be valuable and that value will be assessed under Significance or Approach as appropriate.

Significance

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

Investigator(s)

Are the Core leader, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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)? For the Administrative Core: How well do the core leader's administrative, management, and leadership capabilities provide oversight and direction to the management activities of the core?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

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?

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?

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.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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.

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for 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:

• overall management of the study
• developing and implementing systems necessary for communications among the various study organizational components.
• All data and samples shall be placed in the public domain and shared freely, as a fundamental purpose of this study is the establishment of an unrestricted public database.
• 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 designated NIA Project Scientist will serve as a member of the Executive Committee and have substantial scientific/programmatic involvement during conduct of this cooperative agreement, through technical assistance, advice, and coordination above and beyond normal program stewardship of grants. The awardee agrees to accept assistance from the designated NIA Project Scientist. This person will participate, through the Executive Committee, in the monitoring of issues relating to recruitment, follow-up, and adherence to protocols and will assist in the development and/or adjustment of study protocols. Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• The Executive Committee, comprised of the PD(s)/PI(s) of the cooperative agreement, the leaders of the cores, representatives of the clinical sites, and the NIA Project Scientist, will have primary responsibility for finalizing standard definitions, procedures, and measures common for all the protocols. The Executive committee will meet regularly, as dictated by the needs of the study. Each full member of the Executive Committee will have one vote, and all major scientific decisions will be determined by majority vote of the Executive Committee. Awardee members of the Executive Committee will be required to accept and implement policies approved by the Executive Committee. Subcommittees appointed by the Executive Committee, comprised of appropriate staff from the cores and clinical sites, will be involved in the design of protocols and manuals of operations, and in ongoing functions of the study such as preparation of publications.
• To oversee the allocation and distribution of biological specimens generated from the study, the Executive Committee will nominate members for the Resource Allocation Review Committee (RARC). This group will review applications for use of the biological specimens. The format of the application and criteria for the use of repository biological specimens will be developed by the RARC with advice and approval from the Executive Committee and made available to all potential users. Membership on this committee will rotate periodically according to a procedure developed by the RARC. Final approval of members of the RARC and final approval for disposition of samples to investigators following RARC review will be made by NIA staff.
• The primary governing body of the study will be the Executive Committee, which will have responsibility for the final details of study design and policy decisions and will define the rules regarding access to data and samples.

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 Executive 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: http://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 Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Laurie Ryan, PhD
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: ryanl@mail.nih.gov

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

Katie Ellis
National Institute on Aging (NIA)
Telephone: 301-402-7734
Email: kellis@nia.nih.gov

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

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