Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)
National Institute on Aging (NIA)

Funding Opportunity Title

Small Vessel Vascular Contributions to Cognitive Impairment and Dementia (VCID) Biomarkers Development Projects (UH2/UH3)

Activity Code

UH2/UH3 Phase Innovation Awards Cooperative Agreement

Announcement Type

New

Related Notices

  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)

Funding Opportunity Announcement (FOA) Number

RFA-NS-16-020

Companion Funding Opportunity

RFA-NS-16-019, U24 Resource-Related Research Projects – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.853, 93.866 

Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to support research that evaluates and further develops candidate predictive, diagnostic, target engagement and progression candidate biomarkers of small vessel cerebrovascular disease in human vascular contributions to cognitive impairment and dementia (VCID) and vascular/Alzheimer's mixed dementias. Biomarkers development projects funded under this FOA, with support from the Coordinating Center (RFA-NS-16-019), will: study biomarkers as individual projects and concurrently establish the interactive consortium (UH2, years 1-2); and then work together as a consortium to perform collaborative cross-project multi-disciplinary studies to further evaluate and develop the most promising biomarker candidates (UH3, years 3-5) to the point of being ready for large scale multi-site clinical validation studies including towards FDA qualification of small vessel VCID biomarkers for phase II and phase III clinical trials (to be carried out under future separate funding).

This FOA is only for studies related to human biomarkers; animal or other disease model studies are not responsive to this FOA unless they directly inform like measures that are performed in parallel in humans; additionally, clinical trials are not responsive. 

Key Dates
Posted Date

February 26, 2016

Open Date (Earliest Submission Date)

April 10, 2016

Letter of Intent Due Date(s)

April 10, 2016

Application Due Date(s)

May 10, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this Funding Opportunity Announcement.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

July 2016

Advisory Council Review

August 2016

Earliest Start Date

September 2016

Expiration Date

May 11, 2016

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Table of Contents

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

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

In May of 2013 the National Institute of Neurological Disorders and Stroke (NINDS), with input from the National Institute on Aging (NIA), held an Alzheimer's Disease-Related Dementias Conference in response to the National Plan to Address Alzheimer's Disease. The Conference brought together national and international experts and members of the public to develop research priorities for accelerating the development of therapies for the Alzheimer's disease-related dementias (ADRDs). The ADRD 2013 research recommendations that resulted are part of the National Plan to Address Alzheimer's Disease. This FOA addresses the National Plan's highest priority for human-based research on vascular contributions to cognitive impairment and dementia (VCID): to develop noninvasive markers of key vascular processes related to VCID in Alzheimer's and related dementias. The research program initiated here underscores the need to facilitate the development of biomarkers to improve the efficiency and outcome of Phase II and III clinical trials and advance therapeutic development. These companion FOAs (RFA-NS-16-020, i.e. this FOA; and RFA-NS-16-019 for the Coordinating Center) establish the Small Vessel VCID Biomarkers Consortium, and are focused on small vessel (i.e. arterioles, capillaries, and venules) VCID in vascular cognitive impairment (VCI), vascular dementia, and all mixed and pure cognitive impairment and dementias with contributing small vessel vascular disease, including such as commonly occurs in sporadic Alzheimer's disease. Awards funded under these two FOAs create a consortium and infrastructure to complete development projects as well as planning that will enable follow-up activities, including large scale multi-site validation studies and other activities, for future FDA qualification of small vessel VCID biomarkers and use in clinical trials.

Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on during the planning stage of their application (see Agency contacts, Section VIII). See also Applicant Webinar information under Section IV.7 below ("Other Submission Requirements and Information").

Development Project Objectives

The overall objective is to further develop promising predictive, diagnostic, target engagement and progression candidate biomarkers of small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias to the point of being ready for next steps (to be carried out under future separate funding, including large scale multi-site clinical validation studies toward FDA qualification of small vessel VCID biomarkers for phase II and phase III clinical trials).

During the UH2 phase, individual projects will further develop candidate biomarker/s that they propose in response to the FOA, including by: additional rigorous evaluations; replication; assessment of potential for use in clinical settings; and optimization of protocols and reagents that are "multi-site ready". During the UH2 phase individual biomarkers development projects will work together and with the Coordinating Center (RFA-NS-16-020) to establish collaborative parameters and agreements of the consortium that will be required to enter the UH3 phase, including: committees governing sharing of data and biospecimens as well as publication policies; standardized protocols that will be used in cross-project collaborative UH3 studies; best practices and quality control (Q/C) protocols for data, imaging, and biospecimens; a core set of de-identified clinical data elements, including for cognitive outcomes and assessments that are sensitive to change, or predictive of functional cognitive impairment, for UH3 cross-project collaborative studies; consortium agreements for evaluating biomarkers for consideration for cross-site collaborative development studies during the UH3 phase; consortium guidelines for assessment of strengths and weaknesses of candidate biomarkers; and planning next steps toward biomarkers qualification that are beyond activities covered under this FOA.

One or more biomarkers for which there is a strong scientific rationale to move forward, together with a meritorious research proposal to develop further the biomarker/s, are required for a competitive application to this FOA. Satisfactory progress on each project's UH2 individual research is required for transition from the UH2 into the UH3 phase of the program; however, comparative/competitive (biomarker vs. biomarker) evaluation of development project's candidate biomarker/s will not be a gating decision point. For successful transition from the UH2 to the UH3 phase, individual projects must also demonstrate full and effective participation in establishing the consortium and full vestment in all cross-site collaborative activities such as sharing, transparency, standardization of protocols, and ability to contribute to and execute cross-site research studies and analyses that will be required during the UH3 phase.

Standard NIH sharing policies apply to the full scope of activities supported under this program. In addition, during the UH3 phase, all funded studies will be required to share experimental data and to facilitate sharing of de-identified clinical data and images generated and/or used, including via appropriate informed consent, via the Coordinating Center database. The minimal de-identified clinical data requirement for this will be using the core set of de-identified clinical data elements and all imaging data agreed upon during the UH2 phase. Sharing of original experimental data will be within consortium; sharing of de-identified clinical data and images will be with other members of the consortium (as the data are generated) as well as with researchers that are not part of the consortium (at the time of first publication). For newly generated clinical data in the UH3 phase, an appropriate consent option to facilitate this sharing must be provided to study participants. See further consent guidance below.

For participation in the UH3 phase, it is expected that investigators will facilitate sharing of biospecimens. For biospecimens generated during the UH3 phase, an appropriate consent option to facilitate this sharing is expected to be provided to study participants, including the possibility that biospecimens will be banked in the NINDS biomarkers repository.

All banking costs for utilization of the NINDS Repositories (which will be during the UH3 phase only), other than personnel time/effort for sample and data collection/sharing, will be budgeted under the companion Coordinating Center (RFA-NS-16-019) or otherwise paid for by the NINDS and not included in budgets prepared by applicants to this FOA.

Characteristics of Responsive Applications

This FOA is for studies to develop candidate human biomarkers of small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias. The goal is to develop candidate biomarkers to readiness to enter into (under future separate funding) large scale multi-site clinical validation studies toward FDA qualification for phase II and phase III clinical trials.

Candidate biomarkers proposed for development under this FOA may include predictive, diagnostic, target engagement and progression biomarkers; technical approaches may include imaging, clinical, physiological, biochemical, and fluid-based biomarkers. Affected cerebrovascular small vessels (arterioles, capillaries, and venules) may be in grey matter or white matter. The cerebrovascular lymphatic and glymphatic systems are in scope.

The merit of proposed biomarker candidates will be evaluated in the context of their potential for development under this FOA to the point of readiness for large scale multi-site validation, qualification, and use in clinical trials. Assays proposed to evaluate biomarker candidates, as well as outcome measures, should be quantitative, robust, reproducible, and clearly linked to small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias.

During the UH2 phase, each development project will conduct research independently on their own proposed candidate biomarker/s. Multiple Program Director/Principle Investigator (Multi-PD/PI) applications with more than one site are allowed. This is to ensure that development projects have appropriate interdisciplinary expertise (e.g. imaging, clinical, physiological, and fluid-based biomarkers) as well as adequate access to cohorts. Although it is not a requirement for individual applications to focus on more than one small vessel VCID biomarker modality, individual applications are expected to include a scope of expertise that will contribute the full range of shared consortium responsibilities during both the UH2 and UH3 phases.

While biomarkers for small vessel VCID are the main focus of this program, it is recognized that the vascular tree is a continuum, and large vessel disease biomarkers that clearly relate to and inform small vessel VCID are in scope. Applications that focus mainly or exclusively on large vessels are out of scope.

Additional potential strength would be added by cross-referencing of small vessel VCID candidate biomarkers to biomarkers that are under development or in use for other neurodegenerative disorders (e.g., but not limited to, beta-amyloid and tau). Utilization of specimens and/or imaging data from an established cohort may also be considered a strength.

It is in scope, and encouraged if appropriate, for applications to propose studies that utilize established resources and studies that are ancillary to parent clinical studies.

Characteristics of Non-Responsive Applications

This FOA is only for studies related to human biomarkers; animal or other disease model studies are not responsive to this FOA unless they directly inform like measures that are performed in parallel in humans; additionally, clinical trials as defined by the NIH are not responsive. No epidemiological studies will be supported under this FOA.

Applications proposing screens (e.g. 'omics studies, genome wide association, network biology, etc.) for biomarkers are not responsive; however, 'omics approaches may be used as appropriate to further evaluate and develop proposed candidate biomarkers. Moreover, it is responsive to propose the development of improved biomarkers in a class that has already been associated with VCID, for example but not limited to, imaging and circulating inflammatory biomarkers.

Studies not focused on small vessel VCID and vascular/Alzheimer's mixed dementias are not responsive.

Biospecimens

Biospecimens collected could include, but are not limited to, whole blood, plasma, serum, and cerebrospinal fluid (CSF). Parameters for sharing biospecimens during the UH3 phase are expected to follow NINDS precedents including best practices, for example in the NINDS PDBP Program, but will be further informed by evolution of the field and by Small Vessel VCID Consortium discussions during the UH2 phase of this program. While genetics is not the main focus of this FOA, when possible, applicants are encouraged to make available high quality DNA by submitting blood samples to the NINDS DNA Repository. For DNA collection, the following volume and timelines are expected: whole blood (for DNA extraction; initial visit only): minimum 12 ml (2 filled ACD tubes). Analyses of known relevant genotypes (e.g. ApoE) may be valuable.

In addition to (and not instead of) required sharing, PDs/PIs can propose to collect and store specimens from the same individuals at their institution, including during the UH2 phase and as well as during the UH3 phase of the Program. The PD/PI should spell out how during the UH3 phase any specimens collected in parallel from the same individuals for both NINDS repositories and for institutional banking will be managed and supported. Leveraging pre-existing resources is encouraged. NINDS will not have jurisdiction over specimens collected and stored at institutions using support by other means (i.e. not NINDS funding).

Imaging Based Studies

For applications that include neuroimaging, all formats should be compatible with the Medical Image Processing, Analysis, and Visualization tool (MIPAV:  http://mipav.cit.nih.gov/).

Opportunities for Partnership

Projects involving partnerships with industry, small businesses or non-government organizations are encouraged under this FOA. The policy of the NIH is to make available to the public the results and accomplishments of the activities that it funds.

Small Vessel VCID Biomarkers Consortium

The Small Vessel VCID Biomarkers Consortium will be established by applications funded under this FOA and its companion FOA "Small Vessel VCID Biomarkers Consortium: Coordinating Center; RFA-NS-16-019). The following is a brief description of the Coordinating Center and collaborative activities that will be accomplished by the Consortium.  

Within 1 month of receiving a Notice of Grant Award, the Coordinating Center will begin committee calls (specified below). The Coordinating Center will organize the Consortium Kickoff Meeting to be held within 4 month of receiving a Notice of Grant Award. The Small Vessel VCID Biomarkers Coordinating Center will also organize annual meetings to enable exchange of data and synergy across the consortium.

All projects funded under this FOA must participate in and accept responsibility for driving the scientific objectives (primary responsibility - Development Projects; supporting role - Coordinating Center) and the essential logistic and administrative elements (primary responsibility - Coordinating Center; supporting role - Development Projects).

Members of all consortium committees, except for the External Advisory Committee, will be determined by members of the Consortium and in consultation with the Scientific Project Officer. The External Advisory Committee will be appointed by the NINDS/NIH and applicants must not nominate any members to this committee in their applications. All consortium committees will be administratively driven by the Coordinating Center. Consortium committees include the following and are to be refined by the Consortium during the UH2 phase of the Development Projects:

  • Consortium Kickoff and Annual Meeting Committee (the Coordinating Center is fully responsible for financial, administrative and logistic support of these meetings)
  • Core Standardized Clinical Data Elements Committee, including subcommittees on:
    A. Clinical Data, Physiological Data, and Cognitive Assessments
    B. Imaging Biomarkers Data
    C. Fluid-Based Biomarkers Data
  • Protocol Standardization and Biospecimen Best Practices Committee
  • Sharing Committee
    A. Access to Data (within the Consortium and with others in the field)
    B. Access to Samples (within the Consortium and with others in the field)
    C. Publications (within the Consortium and with others in the field)
  • Consortium Steering Committee
    A. Assessment of strengths and weaknesses of candidate biomarkers for the UH3 phase
    B. Planning next steps beyond activities covered under this FOA, including for large scale multiple site biomarkers validation toward FDA qualification and use in clinical trials
    C. Liaison with related relevant efforts

Considerations for Sharing and Informed Consent:

It is required that all biospecimens and data (collected under funding from this FOA or under other funding, including extant samples and data) used for this research have appropriate informed consent per NIH policy and as mandated by law.

When new biospecimens and clinical data are collected during the UH3 phase, consent must allow all enrolled individuals the opportunity to consent to share, via NINDS repositories, their de-identified samples and data to researchers in academics, not for profits, and industry (for internal research only, for profit use is not allowed). 

Considerations that Consortium investigators should include in consent forms for samples and data collected during year 3 to year 5 are as follows:

  • The sample and de-identified clinical data may be submitted to an NINDS repository or database, research resources supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke
  • The de-identified samples and clinical data will be securely stored at the repository or database
  • No personal identifiers will be sent with samples and data
  • Blood samples may be used for preparation of DNA, plasma, serum, and cells that may be used for cell culture, including stem cells, from which DNA can be prepared; other biological samples may be collected as applicable, for example cerebrospinal fluid
  • The de-identified samples and clinical data can be distributed to scientists for use in research and teaching only, and as such the Repository does not return results to donors
  • The de-identified samples and clinical data could be used for research in any type of disease or genetic factors, not just vascular contributions to cognitive impairment and dementia
  • The de-identified samples (as well as their derivatives) and clinical data will be available for research and teaching purposes to hospitals, universities, not for profit research organizations, and commercial organizations
  • The de-identified samples and clinical data will be used for research only, and will never be distributed for profit
  • There is a risk that someone could use information from the sample submitted, via DNA, to identify the person from which it came if it were matched with another DNA sample provided by that person. However, any user of this sample must agree not to use it for that purpose, and the risk, while real, is small.
  • Individuals have the right to withdraw from this research project at any time. If possible, any samples contributed will be discarded if requested; however, because of the sample masking, NINDS may not always be able to identify which samples were donated by a specific person. Withdrawal from the study will in no way affect access to medical care for which the subject is eligible.

It is expected that any embargo time will follow NINDS guidance (2 years maximum for biospecimens; release at time of relevant publication for data). Following submission to NINDS repositories, samples are subject to NINDS policy and oversight. 

When submitting to relevant NINDS databases and/or repositories, investigators must provide up to date and officially IRB-approved and NINDS-approved (template) consent forms; these forms are the NINDS record of appropriate handling of consent. A copy of the consent form for each subject should be kept on file by the project investigator but does not need to (and should not be) sent with samples and data submitted. 

See Section VIII. Other Information for award authorities and regulations.
Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.   

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NINDS intends to commit up to $5,000,000 in direct costs in FY2016 to fund 5-8 awards.

Award Budget

Application budgets are limited to $750,000 in direct costs per year, and must reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is 5 years. 

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.  

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

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

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

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

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:

Roderick A. Corriveau, Ph.D.
Telephone: 301-496-5680
Fax: 301-480-1080  
Email: roderick.corriveau@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: State the aims and hypotheses to be tested.

Research Strategy: Organize the Research Strategy by Significance, Innovation, and Approach. A Milestone Plan, under separate heading, must be included in the Approach.

Significance: Describe the rationale and supporting data demonstrating the merit of predictive, diagnostic, target engagement or progression candidate biomarker/s of small vessel cerebrovascular disease in human vascular VCID and vascular/Alzheimer's mixed dementias. Describe the rationale and supporting data demonstrating the merit of the technical approaches used to develop candidate biomarker/s, including potential to strongly contribute to cross-consortium studies in the UH3 phase.

Innovation: Describe the leading edge and innovative attributes the application brings to both the specific biomarker candidate/s approach, as well as the overall technical advances and innovative strengths that the application has to offer the consortium. 

Approach: Describe the range of interdisciplinary expertise included that will ensure success in the UH2 phase, and will poise the team for making strong contributions to the UH3 phase. The proposed approach should detail the strengths and appropriateness of assays for candidate biomarkers, plus whether or not assay measures are quantitative, robust, reproducible, and clearly linked to small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias.

In the UH2 phase (years 1-2), during which science will be performed independently by each funded project, address:

  • plans for further development of candidate biomarker/s proposed in response to the FOA including by additional rigorous evaluations, replication, and assessment of potential for use in clinical settings
  • plans for further optimization of protocols and reagents that are transparent, shared, and "multi-site ready"
  • commitment to work with other funded Development Projects investigators and the Coordinating Center during the UH2 phase to establish collaborative elements of the consortium required to enter the UH3 phase; clear statement of not only willingness to collaborate, but also of how this commitment will be implemented
  • the strength and appropriateness of assays proposed to evaluate biomarker candidates, plus whether or not assay measure quantitative, robust, reproducible, and clearly linked to small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias

The UH3 phase (years 3-5) of the Research Strategy should address:

  • commitment, including strategies how, to work with other funded Development Projects investigators and the Coordinating Center to implement collaborative elements of the consortium required to perform collaborative cross-project multi-disciplinary studies to further evaluate and develop biomarker candidates to readiness for the next steps (i.e. ready for large scale multi-site clinical validation, clinical trials, and even FDA qualification)

Milestone Plan: The application must include a Milestone Plan in the Approach with a timeline as indicated below (minimally) and additional milestones to assess achievement of the UH2 phase objectives. Milestones should be unambiguous, quantifiable, and scientifically justified. Milestones are for completion of the first (UH2) phase and readiness for the second phase (UH3). The final Milestone plan is subject to concurrence by the Project Scientist.

  • Active participation in consortium committees by 1 month after Notice of Grant Award.
  • Program Director/Principle Investigator/s will attend and speak at the Consortium Kickoff Meeting to be held within 4 months after Notice of Grant Award.
  • Satisfactory participation in beta-testing with the Coordinating Center Data Core (see RFA-NS-16-019) for real time submission of data from remote within 16 months after Notice of Grant Award.

Letters of Support: If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental or nongovernmental entities, letters of support detailing the terms of collaboration and data sharing must be included, and must be from the appropriate authority/ies (e.g. institutional/foundation official, funding sponsor, and/or lead PI of the parent activity). This letter should also disclose the process of sharing for the parent activity and discuss if sharing of these specimens might extend beyond the individual project and involve collaborative activities within the consortium. Any conflicts in sharing with any known entities should be revealed and discussed. Ancillary studies must not interfere with the parent study and must not place undue burden on participants. Approved procedures and policies from the parent study must be followed and must have patient consents that allow broad sharing of de-identified clinical data, and deposition of biospecimens in the NINDS repositories and databases, as appropriate (for the UH3 phase). Review and approval for the use of samples and data must be completed and a letter of approval must be obtained prior to submission of an application under this FOA.

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. During the UH3 phase, shared clinical data is to be submitted to the Coordinating Center on a real time basis, if real time submission is not possible, then all data must be submitted at least on a quarterly basis. Investigators must plan appropriately for sharing of biospecimens via NINDS repositories during the UH3 phase. For ancillary studies using existing cohorts and infrastructure, broad sharing of de-identified clinical, laboratory data and biospecimens must not be restricted by parent study policy or procedures.
  • Applications must also make a clear administrative and institutional commitment, including strategies how, to share during the UH3 phase de-identified biospecimens, images, and core clinical data elements both within the consortium as well as with other investigators.
  • Commitment, including strategies how, e.g. considering informed consent, personnel, and logistics, to share de-identified biospecimens, images, and core clinical data elements both within the consortium as well as with other investigators.

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

The Appendix should contain the following materials (as appropriate to the study):

  • Study protocol
  • Consent forms

If an ancillary study to an existing project, include also:

  • The protocol for the parent study
  • Investigator's brochure, if applicable, for the parent clinical study
  • Consent forms (for both the parent clinical study and the ancillary studies, if different) 

IRB approval of the informed consent form(s) is not required at the time of submission of the application. However, drafts of informed consent form(s) must be included.

Planned Enrollment Report

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicant Webinar

Applicants are strongly encouraged to consult with NINDS Scientific/Research staff early on during the planning stage of their application (see Agency contacts, Section VIII). This early contact will provide an opportunity to clarify the applicant's understanding of NINDS’ goals, policies and guidelines. These discussions also provide important information and guidance on how to develop an appropriate application that will be subject to peer review under this program.  To facilitate this, an Applicant Webinar will be scheduled to provide an overview of the FOA and answer questions. The webinar is open to all prospective applicants. Participation in the teleconference is not a prerequisite for applying, and is not required for a successful application. Information about how to participate in the webinar will be posted at http://www.ninds.nih.gov. Potential applicants are encouraged to submit their questions or comments to roderick.corriveau@nih.gov prior to the meeting. Afterwards, the webinar slides and a summary of the questions and answers will be posted on the same site. NIH will also post a list of Frequently Asked Questions (FAQs) and answers; this information may be updated without additional notice.

Please notify the NINDS Program Officer by email at roderick.corriveau@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Section V. Application Review Information
1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

The review will emphasize strong rationale and supporting data indicating meritorious candidate/s for predictive, diagnostic, target engagement or progression biomarker/s of small vessel cerebrovascular disease in human vascular VCID and vascular/Alzheimer's mixed dementias.

The review will consider interdisciplinary expertise to ensure success in the UH2 phase that will poise the team for making strong contributions to the UH3 phase.  

Overall Impact

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).

Scored Review Criteria

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

Does the project effectively address the goal of developing promising predictive, diagnostic, target engagement or progression candidate biomarkers of small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias? Are the rationale and supporting date for proposed biomarker candidates strong and supportive of further development?

Investigator(s)

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

Will the PDs/PIs and collaborating investigators bring a range of interdisciplinary expertise regarding small vessel VCID and biomarker development and thus add excellent and synergistic value that will benefit both this application, and the overall consortium?

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?

Does the application include leading edge and innovative attributes to its small vessel VCID biomarker candidate/s development that may benefit the project's individual UH2 phase, as well as the overall goals of the consortium? 

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Are the techniques and assays proposed to develop candidate (predictive, diagnostic, target engagement or progression) biomarkers of small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias biomarker/s appropriate? Are the assays and measures quantitative, robust, reproducible, and clearly linked to small vessel cerebrovascular disease in human VCID and vascular/Alzheimer's mixed dementias?

Does the approach for the UH2 phase ensure optimization of protocols and reagents such that the team will be technically ready to contribute to and participate in UH3 cross-consortium studies? Are the milestones for transition to the UH3 phase suitable?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

Additional Review Criteria

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.

Commitment to Collaborative Interactions:

Does the application make clear scientific, administrative and institutional commitments to collaborate with other researchers and institutions to establish and work within the Small Vessel VCID Consortium?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council. 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.
  • Compliance with data and resource sharing policies.
3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information
1. Award Notices

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

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

For funded applications, the PI will submit a Transition Progress Report (15 pages maximum) to the Program Officer that is due exactly 20 months after the initial Notice of Grant Award is issued. This Transition Progress Report will document progress on UH2 milestone/s and will indicate: (i) readiness of their project to support consortium activities during the UH3 phase, and (ii) readiness of their proposed candidate biomarker/s for entry into collaborative cross-site UH3 studies. Decisions regarding entry into the UH3 phase will be made by the NINDS. The release of UH3 fund will be based successful completion of UH2 milestone/s, program priorities, and availability of funds.

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.

2. Administrative and National Policy Requirements

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

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

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

Determining experimental approaches, designing protocols, and conducting experiments;

  • Submitting annual progress reports during the funding period, in a format as agreed upon by NINDS program staff;
  • Accepting and implementing any other common guidelines and procedures developed for the Small Vessel VCID Biomarkers Consortium initiative and approved by NINDS program staff;
  • Attending Consortium calls and participating actively in Small Vessel VCID Biomarkers Consortium activities;
  • Being willing to serve as a chair or member of the Small Vessel VCID Biomarkers Consortium Steering Committee and other Small Vessel VCID Biomarkers Consortium committees if elected;
  • Attending in-person Small Vessel VCID Biomarkers Consortium meetings (including the initial Kickoff Meeting) once per year organized by the Coordinating Center with input from the NINDS, the Steering Committee, and the Advisory Committee, and present up to date findings (including unpublished results) on ongoing projects.
  • Awardees are expected to make new information and materials known to the research community not only in the annual Consortium meeting but also in a timely manner through publications, web announcements, reports to NINDS program staff, and other mechanisms.
  • Timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgement of NINDS support. Timely publication of major findings is required.

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

NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientist will be to facilitate and not to direct the activities. 

The NINDS Project Scientist will:

  • Contribute to the adjustment of research protocols or approaches as warranted;
  • Serve as a liaison between the awardees, the NINDS Advisory Council and the larger scientific community; 
  • Serve on committees of the Small Vessel VCID Biomarkers Consortium as appropriate;
  • Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
  • Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
  • Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements.

Additionally, an NINDS Program Official 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:

None

Dispute Resolution:

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

Consideration of Development Projects for Transition from the UH2 Phase to the UH3 Phase

At the UH2/UH3 transition point, all Development Projects funded under this FOA must, submit a report (15 pages maximum) to the NINDS Project Officer for consideration for entry into the UH3 phase. This report will document progress on UH2 milestone/s and will indicate: (i) readiness of their project to support consortium activities during the UH3 phase, and (ii) readiness of their proposed candidate biomarker/s for entry into collaborative cross-site UH3 studies. This report will be delivered to the NINDS Project Officer, and is due exactly 20 months after the initial Notice of Grant Award is issued. Decisions regarding entry into the UH3 phase will be made by the NINDS.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

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

Scientific/Research Contact(s)

Roderick A. Corriveau, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: roderick.corriveau@nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone:  301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Tijuanna Decoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: tijuanna.decoster@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.