It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Background

REM sleep behavior disorder (RBD) is a parasomnia that presents with abnormal dream mentation, abnormal behaviors, and increased electromyographic tone on polysomnography during REM sleep. Older individuals with RBD frequently develop neurodegenerative diseases, particularly a-synucleinopathies: Parkinson’s disease (PD), Lewy Body Dementia (LBD), and Multi-System Atrophy (MSA). Individuals with idiopathic RBD (iRBD) develop an overt synucleinopathy at high rates: 40-50% in 5 years and 80-92% in long-term follow up. iRBD provides a unique opportunity to understand the clinical development and evolution of a-synucleinopathies, as well as a potential path for developing disease prevention therapies. While it is not possible at this time to identify whether a person will develop PD, LBD, or MSA, iRBD is a preclinical/prodromal phase of neurodegenerative, particularly a-synucleinopathy, illness. The current iRBD research community includes investigators and centers across North America and the world. There have been attempts to carry out multi-center iRBD research, but interpretation of findings has been complicated by small numbers of iRBD subjects at individual centers; differences in assessment protocols, including collection methods for cognitive and biomarker data; and variability in diagnostic procedures at different centers. This FOA seeks to develop and support a consortium of investigators who will establish a common iRBD research protocol to collect and share harmonized clinical, cognitive, and biomarker data, establishing a centralized repository of biosamples from individuals with iRBD as they progress from prodromal a-synucleinopathy to PD, LBD, or MSA.

Research Scope and Objectives

The PaSS U19 seeks to understand and characterize the preclinical/prodromal phase of a-synucleinopathies. The study will recruit a cohort of iRBD subjects and follow them if/until they convert to PD, LBD, or MSA, using standardized psychometric tests, clinical/neurological evaluations, and diagnostic procedures. PaSS will identify changes associated with the earliest manifestations of a-synucleinopathy disease, including biomarkers of disease progression and potential surrogate endpoints. Biomarkers of a-synucleinopathy burden may range from neurophysiology, to changes in biofluid/tissue, to neuroimaging changes. The eventual goal is to find neuroprotective interventions for a-synucleinopathies.

Applicants should make use of existing infrastructure developed by NIH and advocacy organizations to study Alzheimer's disease, Alzheimer's disease-related dementias, and Parkinson's disease. Data and biosamples collected by PaSS should be readily harmonized with existing data and biosample repositories. Applicants are encouraged to establish collaborations with the Alzheimer's Disease Research Centers (https://www.nia.nih.gov/health/alzheimers-disease-research-centers) and the Michael J. Fox Foundation's Parkinson's Progression Markers Initiative (PPMI) (https://www.michaeljfox.org/ppmi-clinical-study), as well as worldwide collaborations between academic, government, and industry investigators.

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

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.
• o 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.

A multiple-principal investigator (PI) format is required, with one or more PIs with expertise in sleep disorders and one or more PIs with expertise in neurodegenerative diseases, particularly Parkinson’s disease and Lewy Body Dementia

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

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

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

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

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, 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.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Miroslaw (Mack) Mackiewicz, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-594-7636
Fax: 301-496-9350
Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Administrative Core (use component type "Admin Core")	6
Optional Core (use component type "Core")	6
Project	12

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, 1
• Administrative Core: Required, 1
• Optional Core: Optional, 1-9
• Project: Required, 1-9

When preparing your application, 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.

Program Director/Principal Investigator: A multiple-PD/PI format will be required, with one or more PD(s)/PI(s) with expertise in sleep disorders and one or more PD(s)/PI(s) with expertise in neurodegenerative diseases, particularly Parkinson’s disease and Lewy Body Dementia. The PD(s)/PI(s) should be scientific leaders in their respective fields and will coordinate, integrate, and guide all aspects of PaSS, providing creative, scientific, and administrative leadership. Provide any evidence of collaboration and interdisciplinary research among the investigators who will be associated with PaSS. Outline any experience the PD(s)/PI(s) have in the field of iRBD and a-synuclein neurodegenerative diseases. Provide evidence that the PD(s)/PI(s) have demonstrated that they can coordinate, integrate, and provide guidance in the establishment of programs in iRBD research.

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: Describe the overall scientific objective of the application, the individual aims of the project(s), and how individual cores contribute to these aims and the overall objective.

Research Strategy:

Significance. Focusing on PaSS as a whole, address how the concepts, methods, technologies, treatments, services, or preventive interventions that drive this field will be changed if the proposed aims are achieved. Describe any preliminary data on which the project is based.

Approach. Include the major approaches and studies involved in the application, showing how the cores and projects are tightly integrated with each other. Describe the mechanisms that will ensure the coherence of the project and maintain a multidisciplinary focus. The following are some specific issues that applicants must plan for, and that NIA believes must be addressed in PaSS.

• The primary goal is studying presynaptic/prodromal a-synucleinopathy, but iRBD is, itself, an important sleep disorder. Describe how sleep will be studied and characterized in PaSS. Research quality polysomnography (PSG) and characterization of sleep physiology in iRBD subjects at baseline and over time should be part of PaSS.
• Describe how iRBD and any comorbid sleep disorders (e.g., sleep apnea) will be managed, including pharmacological management. PaSS is not meant to be a clinical trial for iRBD treatment, but algorithmic management of iRBD and comorbid sleep disorders should be discussed.
• Discuss management of emergent synucleinopathy symptoms. Participant safety and quality of life must be paramount considerations.
• Discuss how phenoconversion to PD, LBD, or MSA will be managed. Close collaboration with established Alzheimer's Disease Centers (ADCs) and PPMI centers will be important. Dual enrollment and concurrent follow up of subjects in PaSS and PD or LBD natural history studies should be considered and discussed.
• Discuss whether PD or LBD subjects with iRBD will be included in PaSS (e.g., as a comparison group). Discuss inclusion/management of concomitant neurological or psychiatric illness.
• Neuropathological investigations are not an initial aim of this FOA, but the application should describe provisions for autopsy consent as well as postmortem brain collection.
• Standardized, validated assessment of a-synucleinopathy-related signs and symptoms (e.g., UPDRS-MDS and/or NACC's UDS LBD module) are expected, but remote (non-laboratory) digital measures should be discussed and explored.
• A registry of individuals with iRBD but not PaSS subjects (perhaps in collaboration with patient or sleep professional organizations) should be considered.
• Discuss how PaSS will maximize retention of subjects, as well as how it will recruit a racially and socio-economically diverse cohort. Provide evidence that sufficient iRBD subjects are available at clinical sites and outline plans for identifying and recruiting subjects.

Letters of Support: Provide any letters of support specific to the Overall component.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data can be made accessible via open or controlled access, depending on the data type and data source and as determined by the informed consent documents for the study. Applicants are strongly encouraged to follow the data sharing model established by the Alzheimer’s Disease Neuroimaging Initiative (ADNI); see http://adni.loni.usc.edu.

Datasets used/generated by PaSS are expected to be accessible and reusable by qualified individuals via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data--genomic, proteomic, and metabolomic), as appropriate and consistent with achieving the goals of the program. All biological samples obtained or used to generate data by PaSS are expected to be made available to qualified investigators, as appropriate and consistent with achieving the goals of the program. PaSS is expected to utilize NIA-supported repositories (NACC https://www.alz.washington.edu/ , NCRAD https://ncrad.iu.edu/, NIAGADS https://www.niagads.org/ , LONI https://www.loni.usc.edu/, and the AMP-AD Knowledge Portal https://adknowledgeportal.synapse.org/#/) to provide this shared access. Note that costs for biospecimen collection are not included as a component of the NCRAD repository, and some costs for the biospecimen banking will be borne by grantees utilizing NCRAD. Similarly, costs for neuroimaging data storage and sharing are not included as a component of the LONI repository. Applicants should consult with NCRAD and LONI staff when planning the application budget. Applicants may request funds to curate data and resources to prepare them for sharing and for other costs associated with sharing.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

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

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

In addition to the required content of the Protection of Human Subjects attachment, describe the procedures for obtaining informed consent for: 1) research on cognitively-impaired individuals who may not have the capacity to consent--specifically, how proxy or surrogate consent will be obtained in the context of local and state law; 2) future participation in research studies if the participant becomes unable to consent (advanced directive for research); and 3) sharing data and specimens with other qualified scientists (including from for-profit organizations) consistent with achieving the goals of this program. Attention should be paid to obtaining advanced directives for research, obtaining autopsy permission from participants and families, and informed consent for current and future use of biological samples by qualified investigators. Consent should be obtained from participants for sharing of cells, DNA, and other biological samples, as well as genetic and phenotypic information. Consent should be obtained from participants for storage in repositories and distribution from those repositories.

See the Biospecimen Task Force guidelines on the NACC web site: https://www.alz.washington.edu/BiospecimenTaskForce.html

For further guidance on consent forms, see the NCRAD sample consent form language: https://ncrad.iu.edu/recommended_consent_language.html

For sample language regarding genetics that may be used in consent forms, see:

http://www.nia.nih.gov/research/dn/sharing-policy-and-guidance-research-genetics-alzheimers-disease

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.

When preparing your application, 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 Administrative 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 the program project, and the aims of the core should show the elements by which leadership and integration will be achieved. If proposing an external advisory board, do not list proposed members in the application. Instead, list intended areas of expertise.

Research Strategy:

Significance. Describe how the activities of the Administrative Core will implement the overall vision of PaSS as an integrated investigation.

Approach. Describe how the several elements proposed in the Administrative Core will be operationalized to achieve transparent communication across projects and cores, cross-project collaboration, and common objectives for the project as a whole. Elements should include, but not be limited to, means for internal quality control of research, management of day-to-day project activities, management of contractual agreements, resolution of disputes, allocation of funds, and plans for joint dissemination of study results.

Applicants must document the availability and number of iRBD subjects available at clinical sites (based on historical data) and describe how subjects will be identified and recruited.

Function and intended areas of expertise of an external advisory board should be described here.

Letters of Support: Do not provide letters of support from proposed External Advisory Board members.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data can be made accessible via open or controlled access, depending on the data type and data source and as determined by the informed consent documents for the study. Applicants are strongly encouraged to follow the data sharing model established by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (see http://adni.loni.usc.edu).

Datasets used/generated by PaSS are expected to be accessible and reusable by qualified individuals via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data--genomic, proteomic, and metabolomic), as appropriate and consistent with achieving the goals of the program. All biological samples obtained or used to generate data by PaSS are expected to be made available to qualified investigators, as appropriate and consistent with achieving the goals of the program. PaSS is expected to utilize NIA-supported repositories (NACC https://www.alz.washington.edu/ , NCRAD https://ncrad.iu.edu/, NIAGADS https://www.niagads.org/ , LONI https://www.loni.usc.edu/, and the AMP-AD Knowledge Portal https://adknowledgeportal.synapse.org/#/) to provide this shared access. Note that costs for biospecimen collection are not included as a component of the NCRAD repository, and some costs for the biospecimen banking will be borne by grantees utilizing NCRAD. Similarly, costs for neuroimaging data storage and sharing are not included as a component of the LONI repository. Applicants should consult with NCRAD and LONI staff when planning the application budget. Applicants may request funds to curate data and resources to prepare them for sharing and for other costs associated with sharing.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

In addition to the required content of the Protection of Human Subjects attachment, describe the procedures for obtaining informed consent for: 1) research on cognitively-impaired individuals who may not have the capacity to consent--specifically, how proxy or surrogate consent will be obtained in the context of local and state law; 2) future participation in research studies if the participant becomes unable to consent (advanced directive for research); and 3) sharing data and specimens with other qualified scientists (including from for-profit organizations) consistent with achieving the goals of this program. Attention should be paid to obtaining advanced directives for research and obtaining autopsy permission from participants and families and informed consent for current and future use of biological samples by qualified investigators. Permission should be obtained for sharing of cells, DNA, and other biological samples, as well as genetic and phenotypic information. Permission should also be obtained for storage in repositories and distribution from those repositories.

See the Biospecimen Task Force guidelines on the NACC web site: https://www.alz.washington.edu/BiospecimenTaskForce.html

For further guidance on consent forms see the NCRAD sample consent form language, see: https://ncrad.iu.edu/recommended_consent_language.html

For sample language regarding genetics that may be used in consent forms, see:

http://www.nia.nih.gov/research/dn/sharing-policy-and-guidance-research-genetics-alzheimers-disease

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.

When preparing your application, 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 (Optional Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Optional Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Optional 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) (Optional 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 (Optional 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 (Optional 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 (Optional Core)

Specific Aims: Identify with which projects the core will assist and the role of the core in PaSS.

Research Strategy:

Organize the Research Strategy into sections on a) Significance and b) Approach. Innovation will be considered in relation to Approach and Significance.

Letters of Support: Provide any letters of support that are specific to the relevant core.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for the study. Applicants are strongly encouraged to follow the data sharing model established by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) http://adni.loni.usc.edu.

Datasets used/generated by PaSS are expected to be accessible and reusable by qualified individuals via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data--genomic, proteomic, and metabolomic), as appropriate and consistent with achieving the goals of the program. All biological samples obtained or used to generate data by PaSS are expected to be made available to qualified investigators, as appropriate and consistent with achieving the goals of the program. PaSS is expected to utilize NIA-supported repositories (NACC https://www.alz.washington.edu/ , NCRAD https://ncrad.iu.edu/, NIAGADS https://www.niagads.org/ , LONI https://www.loni.usc.edu/, and the AMP-AD Knowledge Portal https://adknowledgeportal.synapse.org/#/) to provide this shared access. Note that costs for biospecimen collection are not included as a component of the NCRAD repository, and some costs for the biospecimen banking will be borne by grantees utilizing NCRAD. Similarly, costs for neuroimaging data storage and sharing are not included as a component of the LONI repository. Applicants should consult with NCRAD and LONI staff when planning the application budget. Applicants may request funds to curate data and resources to prepare them for sharing and for other costs associated with sharing.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Optional Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

In addition to the required content of the Protection of Human Subjects attachment, describe the procedures for obtaining informed consent for: 1) research on cognitively-impaired individuals who may not have the capacity to consent--specifically, how proxy or surrogate consent will be obtained in the context of local and state law; 2) future participation in research studies if the participant becomes unable to consent (advanced directive for research); and 3) sharing data and specimens with other qualified scientists (including from for-profit organizations) consistent with achieving the goals of this program. Attention should be paid to obtaining advanced directives for research and obtaining autopsy permission from participants and families and informed consent for current and future use of biological samples by qualified investigators. Permission should be obtained for sharing of cells, DNA, and other biological samples, as well as genetic and phenotypic information. Permission should also be obtained for storage in repositories and distribution from those repositories.

See the Biospecimen Task Force guidelines on the NACC web site: https://www.alz.washington.edu/BiospecimenTaskForce.html

For further guidance on consent forms see the NCRAD sample consent form language: https://ncrad.iu.edu/recommended_consent_language.html

For sample language regarding genetics that may be used in consent forms see:

http://www.nia.nih.gov/research/dn/sharing-policy-and-guidance-research-genetics-alzheimers-disease

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

When preparing your application, use Component Type Project.

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

SF424 (R&R) Cover (Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Project)

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) (Project)

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 (Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project 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 (Project)

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 (Project)

Specific Aims: Describe the aims of the project in relation to the goals of PaSS.

Research Strategy:

The Significance section should include discussion of how this project relates to the goals of the overall project and the preliminary data on which the project is based. If the same study will be conducted across multiple sites, such as clinical or study sites using the same protocol, describe the study once in this section and indicate the sites where the protocol will be carried out.

Letters of Support: Provide any letters of support that are specific to the project.

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

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Data can be made accessible via open or controlled access depending on the data type and data source and as determined by the informed consent documents for the study. Applicants are strongly encouraged to follow the data sharing model established by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (http://adni.loni.usc.edu).

Datasets used/generated by PaSS are expected to be accessible and reusable by qualified individuals via web-based resources with the capacity to store large and diverse datasets (such as data about clinical phenotypes and high-dimensional omic data--genomic, proteomic, and metabolomic), as appropriate and consistent with achieving the goals of the program. All biological samples obtained or used to generate data by PaSS are expected to be made available to qualified investigators, as appropriate and consistent with achieving the goals of the program. PaSS is expected to utilize NIA-supported repositories (NACC https://www.alz.washington.edu/ , NCRAD https://ncrad.iu.edu/, NIAGADS https://www.niagads.org/ , LONI https://www.loni.usc.edu/, and the AMP-AD Knowledge Portal https://adknowledgeportal.synapse.org/#/) to provide this shared access. Note that costs for biospecimen collection are not included as a component of the NCRAD repository, and some costs for the biospecimen banking will be borne by grantees utilizing NCRAD. Similarly, costs for neuroimaging data storage and sharing are not included as a component of the LONI repository. Applicants should consult with NCRAD and LONI staff when planning the application budget. Applicants may request funds to curate data and resources to prepare them for sharing and for other costs associated with sharing.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 3 - Protection and Monitoring Plans

3.1 Protection of Human Subjects

In addition to the required content of the Protection of Human Subjects attachment, describe the procedures for obtaining informed consent for: 1) research on cognitively-impaired individuals who may not have the capacity to consent, specifically how proxy or surrogate consent will be obtained in the context of local and state law; 2) future participation in research studies if the participant becomes unable to consent (advanced directive for research); and 3) sharing data and specimens with other qualified scientists (including from for-profit organizations) consistent with achieving the goals of this program. Attention should be paid to obtaining advanced directives for research and obtaining autopsy permission from participants and families and informed consent for current and future use of biological samples by qualified investigators. Permission should be obtained for sharing of cells, DNA, and other biological samples, as well as genetic and phenotypic information. Permission should also be obtained for storage in repositories and distribution from those repositories.

See the Biospecimen Task Force guidelines on the NACC web site: https://www.alz.washington.edu/BiospecimenTaskForce.html

For further guidance on consent forms see the NCRAD sample consent form language, see: https://ncrad.iu.edu/recommended_consent_language.html

For sample language regarding genetics that may be used in consent forms, see:

http://www.nia.nih.gov/research/dn/sharing-policy-and-guidance-research-genetics-alzheimers-disease

Delayed Onset Study

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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 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) 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 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.

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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

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

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

How well does PaSS improve scientific knowledge, technical capability, and/or clinical practice? Will the concepts, methods, technologies, treatments, services, or preventive interventions that drive this field be changed if the proposed aims are achieved? How strong are the preliminary data on which the project is based?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

How well do the investigators and staff provide creative, scientific, and administrative leadership of PaSS? Is there evidence of collaboration and interdisciplinary research among the investigators who will be associated with PaSS? Are the PD(s)/PI(s) scientific leaders experienced in the field of iRBD and a-synuclein neurodegenerative diseases? Have the PD(s)/PI(s) demonstrated that they can coordinate, integrate, and provide guidance in the establishment of programs in iRBD research?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD(s)/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

How well does PaSS and its components demonstrate the capacity to develop critical new knowledge and unique and innovative contributions to iRBD and a-synuclein neurodegenerative diseases research?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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

How well does PaSS demonstrate appropriate organization and core management? Are there plans to adequately manage specific requirements imposed on PaSS such as sleep studies, pharmacological management of iRBD patients and their management after phenoconversion, inclusion/exclusion criteria, and neuropathological studies? Are organizational plans and management structures adequate to meet the longitudinal goals of PaSS? Are there sufficient iRBD subjects available at clinical sites (based on historical data) and are plans for identifying and recruiting subjects adequate?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

How adequate are the relevant facilities for the proposed work? Does the geographic relationship between facilities seem reasonable to carry out the proposed work? How capable are the environment and core resources of enhancing cutting-edge research by bringing together multidisciplinary investigators? What are the assurances from institutional leaders that they will provide long-term, stable support and facilitate research?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not Applicable

Not Applicable

Not Applicable

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

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 .

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

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

• Reviewers will consider the following criteria in the determination of an overall impact score for the Administrative Core, although scores for the individual criterion will not be provided. Is the administrative and organizational structure clearly defined, and is it appropriate and adequate to accomplish the objectives of the overall program?
• Is the management plan for fiscal accountability and communication appropriate to facilitate attainment of the objectives of the proposed overall program?
• Are plans to leverage existing government-funded resources included for the benefit of the
• overall program?
• Are the experience, level of commitment, and availability of the Administrative Core Lead adequate to manage the overall program?
• Are the plans for coordination, problem identification and resolution, and the establishment of a strong collaborative environment for the overall program appropriate?

• Reviewers will consider the following criteria in the determination of an overall impact score for the Optional Core, although scores for the individual criterion will not be provided. Is the proposed Optional Core(s) justified and relevant to the theme of the overall program?
• Is adequate justification provided that each Optional Core will support the proposed research project(s)?
• Are the proposed personnel appropriate to lead and staff the core? Are the experience, level of commitment, and availability of the Core Lead adequate?
• Are the relevant facilities and/or services provided appropriate for the activities proposed (including procedures, techniques, quality control), and are the criteria for prioritizing requests for services appropriate?

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 the 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 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 (https://grants.nih.gov/grants/peer/guidelines_general/Guidelines_for_the_Review_of_the_Human_Subjects.pdf).

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 (https://grants.nih.gov/grants/peer/guidelines_general/Review_Human_subjects_Inclusion.pdf).

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 (https://grants.nih.gov/grants/olaw/VASchecklist.pdf).

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

Not Applicable

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 (//grants.nih.gov/grants/guide/url_redirect.htm?id=11151); 2) Sharing Model Organisms (//grants.nih.gov/grants/guide/url_redirect.htm?id=11152); and 3) Genomic Data Sharing Plan (//grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html).

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.

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?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications proposing clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage, and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications proposing clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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

• the protection of human subjects from research risks, and
• 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?

In addition, for applications proposing clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications proposing clinical trials

If proposed, are the administrative, data coordinating, enrollment, and laboratory/testing centers appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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 (https://grants.nih.gov/grants/peer/guidelines_general/Guidelines_for_the_Review_of_the_Human_Subjects.pdf).

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 (https://grants.nih.gov/grants/peer/guidelines_general/Review_Human_subjects_Inclusion.pdf).

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 (https://grants.nih.gov/grants/olaw/VASchecklist.pdf).

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

Not Applicable

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 (//grants.nih.gov/grants/guide/url_redirect.htm?id=11151); 2) Sharing Model Organisms (//grants.nih.gov/grants/guide/url_redirect.htm?id=11152); and 3) Genomic Data Sharing Plan (//grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html).

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

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

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

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

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

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

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

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

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

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

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see 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.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR 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.
• Placing data in the public domain and sharing freely, as appropriate and consistent with achieving the goals of the program, 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.
• 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.
• Participate, through the Executive Committee, in the monitoring of issues relating to recruitment, follow-up, and adherence to protocols.
• 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), 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 RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission 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: [email protected] (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: [email protected]

Miroslaw (Mack) Mackiewicz, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-594-7636
Email: [email protected]

John Hsiao, MD
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: [email protected]

Debra Babcock, Ph.D., MD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email: [email protected]

Ramesh Vemuri, PhD
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Priscilla Garner
National Institute on Aging (NIA)
Telephone: 301-402-7700
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: [email protected]

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.