Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
U24 Resource-Related Research Projects – Cooperative Agreements
None
The purpose of this funding opportunity announcement (FOA) is to have an open competition to support a Coordinating Center for the next phase of the NINDS small vessel vascular contributions to cognitive impairment and dementia (VCID) biomarkers consortium. The original consortium was established under RFA-NS-16-019 and RFA-NS-16-020. The goal of the next phase, under this FOA (Coordinating Center) and RFA-NS-21-005 (sites), is to complete clinical validation of biomarkers initially developed during the first 5-year funding cycle of this program. The Coordinating Center will consist of: (i) an Administrative Core responsible for organizing, coordinating and administratively driving Consortium activities; and (ii) a Data Core that will coordinate, receive, collect, and share data, including de-identified clinical data. The Coordinating Center provides infrastructure and expertise to drive the consortium administratively and contribute scientifically to validation of biomarkers with specified context of use for future clinical trials, including in large phase III trials, with general and diverse populations, and for generating scientific breakthroughs in our understanding and treatment of VCID.
October 12, 2021
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| November 12, 2021 | November 12, 2021 | Not Applicable | March 2022 | May 2022 | July 2022 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
In 2013, 2016, and 2019 the National Institute of Neurological Disorders and Stroke (NINDS), with input from the National Institute on Aging (NIA), held Alzheimer’s Disease-Related Dementias Summits in response to the National Plan to Address Alzheimer's Disease. The Summits brought together national and international experts and members of the public to set research priorities for accelerating the development of therapies for the Alzheimer's disease-related dementias (ADRDs), including vascular contributions to cognitive impairment and dementia (VCID). The ADRD Summit 2019 research recommendations that resulted are now implementation milestones in the National Plan to Address Alzheimer's Disease, updating the ADRD implementation milestones from the 2016 and 2013 ADRD Summits. This FOA addresses the National Plan's highest priority for human-based research on VCID: to develop biomarkers of key vascular processes related to VCID. The research program supported by this initiative underscores the need to develop biomarkers that will facilitate therapeutic development by improving the efficiency, design and outcome of clinical trials, including large-scale phase III trials.
This FOA (RFA-NS-22-017, for the Coordinating Center) and RFA-NS-21-005 (for the sites), together continue the VCID biomarkers consortium established under RFA-NS-16-019 and RFA-NS-16-020. Awards funded under these companion FOAs will provide expertise and infrastructure to complete rigorous clinical validation for up to 6 of 11 candidate VCID biomarkers initially developed by the consortium during the previous 5 years (see https://markvcid.partners.org/). The NINDS will, in a separate process, select and rank-order prioritize the most promising of these candidate biomarkers. The NINDS will work with grantees to determine the number of prioritized biomarkers that will move forward into multi-site clinical validation based on resources, expertise, and power analyses. The Coordinating Center provides infrastructure and expertise to drive the consortium administratively and contribute scientifically to completing clinical validation of NINDS-selected small vessel VCID biomarkers to readiness for use in clinical trials (all phases), including in diverse populations. The FDA defines clinical validation as establishing that the biomarker acceptably identifies, measures, or predicts the concept of interest. With respect to regulatory considerations, the concept of interest is the aspect of an individual’s experience or clinical, biological, physical, or functional state that the biomarker is intended to capture or reflect.
Applicants are to plan for up to 6 biomarkers to move forward. However, at the time of award and implementation the actual number may be lower or higher depending on protocols, resources, and scientific justification. At the conclusion of the next five years each clinically validated small vessel VCID biomarker should have: no or minimal legal (e.g. IP, licensing) or logistic (e.g. cost, invasiveness) barriers to widespread use; a designated category and context of use as defined by the FDA; and a finalized public protocol that describes all details needed to utilize the biomarker independently including but not limited to a biomarker measure, specified cognitive data, and specified other clinical data. This program is intended to fully prepare small vessel VCID biomarkers for integration into and widespread use in clinical trials (all phases) including in large-scale late phase clinical trials in general and diverse populations in the United States (at a minimum African American, Hispanic, and Caucasian populations). Applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on during the planning stage of their application (see Agency contacts, Section VII).
Coordinating Center Objectives
The NINDS small vessel VCID Biomarkers Consortium Coordinating Center will provide a common support infrastructure that is essential for the goals of this program. The Coordinating Center will include an Administrative Core, a Data Core, and a proposal to manage consortium activities during the next five years. The Coordinating Center will be responsible for coordinating, driving, and facilitating data sharing for the consortium, both within and external to the consortium. NIH/NINDS sharing policies are expected to be followed throughout the project. The Coordinating Center will be expected to maintain the necessary infrastructure and service-oriented staff with top level expertise for all necessary information technology and clinical database development and implementation. Ideally, the Coordinating Center will also include staff with high competency and understanding of other aspects of the small vessel VCID biomarkers consortium needed to be a valuable and active collaborator in, for example: human subjects considerations; clinical data relevant to small vessel VCID; statistical analyses including for power and data analyses; biological samples and imaging for biomarker discovery; control data; data and protocol standardization; and protocol implementation including for electronic submission of data, webcatalog development for distribution of data, and relevant best practices. The application will address the following central objectives: (i) seamlessly continue protocols and best practices already established by the NINDS small vessel VCID biomarkers consortium (see https://markvcid.partners.org/); (ii) organize and convene committees, subcommittees, and meetings; (iii) coordinate clinical research including biomarkers selected by the NINDS for validation during the next phase of this program; (iii) receive, house, and make available clinical data for sharing within and beyond the consortium; (iv) serve as a coordinating resource and portal for sharing collected biospecimens within and beyond the consortium; (v) establish and execute a long term, including legacy, sharing plan for samples and clinical data obtained by the consortium.
The timing of Coordinating Center activities will be in parallel with the timing of sites which will perform and complete multi-site clinical validation of promising biomarkers. The goal is to further advance biomarkers initially developed by the consortium during the first 5-year funding cycle to deliver high-quality instrumentally, biologically and clinically validated biomarkers, with a specified category and context of use for each as defined by the FDA, that are ready for use in clinical trials, and for generating scientific breakthroughs in our understanding and treatment of VCID.
Administrative Core
The Small Vessel VCID Biomarkers Coordinating Center Administrative Core will serve as the consortium's information, data, and administrative hub, will organize all committees, subcommittees, and meetings, and will work closely with the NINDS Project Officers as well as the NINDS small vessel VCID biomarkers consortium sites. The Administrative Core will organize, coordinate and administratively drive consortium activities including: establishing the steering committee and five subcommittees (Clinical Data, Physiological Data and Cognitive Assessments; Imaging-Based Biomarkers; Fluid-Based Biomarkers; Protocol Operations and Standardization; Sharing)(the External Advisory Committee will be established by the NINDS); driving the logistics of committee activities including, for example, scheduling, soliciting agenda items, finalizing and distributing agendas, arranging calls including conference calls, minutes (drafting, editing based on Consortium input, and finalizing), and conflict resolution; establishing a core set of clinical data elements (all submitted clinical data shall be de-identified), including for cognitive outcomes and assessments that are sensitive to change, or predictive of functional cognitive impairment; all logistic and financial requirements for annual consortium meetings including if applicable meeting space, accommodation, travel for the contact PD/PIs and up to 2 other key personnel for each site, per diem reimbursement, etc.; required sharing activities including providing support and advice to Validation Sites on informed consent and for coordinating NINDS repositories as needed.
Data Core
The Data Core will establish, maintain, and modify as needed infrastructure to collect (including for real time data entry), curate for quality (e.g. accuracy, completeness, and internal consistency), display, house, and distribute (within the consortium and with external scientists after appropriate publication) data, including de-identified clinical data and imaging data. Once established, the Data Core will build into its infrastructure the core set of de-identified clinical data elements agreed upon by the Consortium. The Data Core will provide full instructions and support for submitting data, and for obtaining data from the Core. The Data Core will include statistical expertise to support and critically evaluate human subjects VCID biomarker validation studies.
Considerations for sharing and informed consent
It is required that all biospecimens and data collected and/or used for research under funding from this FOA (including extant samples) have appropriate informed consent per NIH policy and as mandated by law.
The informed consent process 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 are as follows:
It is expected that any embargo time will follow NINDS guidance (2 years maximum for biospecimens with diagnosis and demographic data; release at time of relevant publication for other clinical data). Samples and clinical data collected in this program are subject to NINDS policy and oversight.
When submitting to relevant NINDS database 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.
Applications Not Responsive to this FOA
Applications that include vertebrate animal research are not responsive to this FOA.
See Section VIII. Other Information for award authorities and regulations.
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. See Section VI.2 for additional information about the substantial involvement for this FOA.
Renewal (RFA-NS-16-019)
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NINDS intends to commit $2,000,000 in FY 2022 to fund one award.
Up to five years.
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
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:
Roderick A. Corriveau, Ph.D.
Telephone: 301-496-5680
Email:[email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Investigators:
The PDs/PIs should have experience and technical excellence in communication in large scale geographically dispersed consortia in neurological and/or biomarkers research, and in informed consent that will ensure successful leadership of the Coordinating Center. PDs/PIs should have proven success facilitating collaborative interactions, e.g. data requests, harmonization, transfer, sharing of data (collecting, banking, receiving, curating, distributing de-identified clinical data), samples and protocols with other investigators and other databases (e.g. but not limited to DISCOVERY, dbGAP, PDBP, LONI, NACC, NINDS Repositories, and NCRAD) that support research in neurological disorders including AD/ADRD disorders.
The Administrative Core and the Data Core should each include experienced personnel with a proposed point of contact identified as key personnel for each Core (one each for the Administrative and Data Cores, respectively) with appropriate training and/or experience with both the IT and the biological/clinical data/scientific/project management subject matters that are essential to the success of this consortium. It is also critical to the success of the small vessel VCID Biomarkers consortium that the two Cores (Administrative and Data) interact effectively with the Biomarkers Validation Projects, the NINDS, as well as with each other. Therefore, in addition to strong leadership and staff with highly specialized expertise needed for each Core, both the Administrative Core and the Data Core must include one dedicated staff member as Key Personnel on the application who: (i) commits six person months per year to the Core, (ii) will be the point of contact for their respective Core; and (ii) is highly motivated, has excellent communications skills, and has significant training and/or experience with both the IT and the biological/clinical data/scientific subject matters that are essential to the success of this consortium.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
The budget must reflect the actual needs of the proposed project. To plan for potential in person meetings with personnel from the consortium sites (Kickoff and Annual meetings) the Coordinating Center (this FOA, RFA-NS-22-017) will budget all funds for all activities (travel, lodging, food) associated with and for the contact PD/PI and up to 2 other key personnel from each of the up to 9 consortium sites (RFA-NS-21-005). .
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: Organize the Research Strategy by Significance, Innovation, and Approach. A milestone plan, under separate heading, must be included in the approach. Applicants are to clearly document, including with examples, how the Coordinating Center will provide infrastructure and expertise to drive the consortium administratively and contribute scientifically to validation of biomarkers; accordingly applicants are not to propose specific biomarkers or biomarker experiments to be performed during the next five years of this program.
Significance: Describe how the proposed Coordinating Center is poised to play a leadership role in the next phase of the NINDS small vessel VCID biomarkers program based on: understanding of and a clear strategy to implement the goals of the FOA; and a clear structure to advance multi-site VCID biomarkers clinical validation studies including by effective plans for leadership, meeting milestones and other deadlines, and for making meaningful contributions to development, refinement, design and interpretation of appropriately powered multi-site biomarker studies.
Innovation: Describe the leading edge and innovative attributes that the proposed Coordinating Center offers the consortium, for example in IT, data management, communication strategies, approaches to organization of meetings and conference calls, and other activities that are the responsibility of the Coordinating Center. The application should provide evidence of harmonization of data across platforms for metanalyses, and harmonization to the extent possible across other large VCID and related dementia studies.
Approach: The Approach section should be organized by Administrative Core, Data Core, and Milestone Plan. The approach should address administrative commitment, VCID experience including in supporting national consortium-based multi-site VCID biomarkers research, and technical ability, to carry out the functions of the Coordinating Center to provide a common support infrastructure that is essential to the goals of the small vessel VCID biomarkers validation consortium. The Approach should address the Coordinating Center’s ability to coordinate consortium activities for both fluid-based and imaging-based VCID biomarkers. Finally, and critically, the approach should detail a plan for an efficient transition from the infrastructure of the current NINDS small vessel VCID consortium to the new award.
Administrative Core: The Administrative Core is responsible for, and this section of the application should describe, the overall management plan and organizational hierarchy of the Coordinating Center and the consortium overall, including its administrative structure, the communication plan, and the conflict resolution plan. Describe how the Administrative Core will organize, coordinate and administratively drive consortium activities including: establishing all committees (Steering Committee as well as committees for Clinical Data, Physiological Data and Cognitive Assessments; Imaging-Based Biomarkers; Fluid-Based Biomarkers; Protocol Operations and Standardization; Sharing [data, samples, publication])(not the External Advisory Committee, which will be established by the NINDS); logistical components of committee activities including, for example, scheduling and holding meetings, soliciting agenda items, decision making, finalizing and distributing agendas, arranging calls including conference calls, minutes (drafting, editing based on consortium input, and finalizing); establishing a core set of standardized VCID clinical data elements to be used for harmonized and sharing, including for cognitive outcomes and assessments that are sensitive to change, or predictive of functional cognitive impairment; all logistic and financial requirements for in person consortium meetings including meeting space, accommodation, travel, per diem reimbursement, etc.; required sharing activities including publication as well as providing support and advice to Validation Sites on informed consent and for coordinating with NINDS repositories. The application should describe how the Administrative Core will work with multiple and de-centralized investigators and end users, schedule large (dozens of participants) interactive and possibly international conference calls including virtually. Describe how the Administrative Core will establish and drive all meetings and Committees, in consultation with the NINDS Scientific Project Officer. Indicate how consortium members (from both the Validation Sites and the Coordinating Center) will be selected for Committees by nomination and vote (NINDS/NIH will be represented on Committees as well).
Data Core: Describe how the Data Core will establish infrastructure, including for real time data entry, to collect, curate for quality (e.g. accuracy, completeness, and internal consistency), display, house, and distribute (within the consortium and with external scientists after appropriate publication) data, including de-identified clinical data, imaging data, longitudinal data, pathological data when applicable, and all relevant control data. Indicate how the Data Core will facilitate efficient and accurate incorporation of new and/or extant clinical data via electronic data entry from remote locations. Indicate how the Data Core will build into its infrastructure the core set of de-identified clinical data elements agreed upon by the consortium. Detail how the Data Core will provide full instructions and support for submitting data, and for obtaining data from the Core. Indicate how the Data Core capacity will meet needs for banking data from on the scale of 2000 individuals, on the order of 250 data elements per individual record, up to 3 clinical data collections (records) per individual per year, plus imaging data (e.g. MRI, DTI) up to twice per year. Indicate how the Data Core will receive in real time or at least quarterly, and by remote electronic submission, data from up to 12 sites per year, and distribute data to approximately the same number. Detail how the data core will harmonize compatible but not identically coded extant data across platforms for sharing and metanalyses. The application should explain the Data Core's statistical expertise by naming personnel to help inform study design, power analyses and data analyses. Applications must detail how standardization of imaging will be harmonized across validation sites, across common imaging hardware, and to the extent possible broadly across the field, in particular with VCID and other related AD/ADRD clinical research.
Milestone Plan: The application must include a Milestone Plan in the approach section with a timeline for establishing the Administrative Core and the Data Core to full functionality as indicated below (minimally). The timeline and milestones will be used to evaluate applications both in peer review and also in consideration of the awarded Coordinating Center for funding of non-competing award years. See the section below on Cooperative Agreement Terms and Conditions of Award for specific guidance on content and timing of Milestones. The final Milestone plan is subject to concurrence by the Project Officer.
The Administrative Core will initiate call to organize committees by 1 month after Notice of Grant Award.
The Administrative Core will establish consortium committees (except the External Advisory Committee, which will be established by the NINDS) by nomination and vote, which will be formed by 4 months after Notice of Grant Award. Consortium committees will include members from both the Validation Sites and the Coordinating Center, as well as representation from the NINDS.
The Administrative Core will organize the consortium kickoff meeting to be held within 4 months of receiving a Notice of Grant Award.
The Administrative Core will organize Annual meetings (1 per year within a month of annual date of original Notice of Grant Award) to enable exchange of data and synergy across the consortium.
The Administrative Core will administratively drive establishment and continued development and updating of a core set of small vessel VCID clinical data elements (next update to be complete by 1 year after notice of grant award) including for cognitive outcomes. This set of clinical data elements will be shared via publication by 2 years after Notice of Grant Award.
The Administrative Core will develop, coordinate and implement process and solutions surrounding informed consent (by 6 months after notice of grant award).
The Administrative Core will facilitate communication and interaction with other relevant VCID, neurodegeneration, and general biomarkers activities including specific studies as well as industry and agencies that can inform successful approaches to biomarker validation and incorporation of biomarkers into late phase clinical trials and wide acceptance and use in academic research, by industry, and for clinical use (by 6 months after notice of grant award).
The Data Core's IT infrastructure for receiving real time data entry from multiple remote locations (including the core set of de-identified VCID clinical data) will be fully functional and successfully beta-tested by the end of year 1.
Data Core will prepare materials for and be fully ready to implement data entry training by 6 months after notice of award and will document completed training of at least 2 named key personnel per validation site by 1 year after award.
The Data Core's IT infrastructure and SOPs for sharing (both with the consortium and external to the consortium) all submitted data from the Biomarkers Validation Sites will be fully functional by the end of year 1. The sharing infrastructure must be able to facilitate sharing of protocols, data, and biosamples within the consortium and also with scientists outside of the consortium.
Letters of Support: If an application plans to utilize the infrastructure or resources of existing activities, letters of support from the project leadership and co-signed by appropriate official signing authority, as appropriate, detailing approval, feasibility, terms of collaboration and data sharing must be included. If applicable, informed consent forms for any parent clinical study and any relevant ancillary studies should be included as part of the appendix.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
If applicable, informed consent forms for any parent clinical study and any relevant ancillary studies should be included as part of the appendix.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the proposed Center address the needs of the research consortium that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research consortium?
To what extent does the application describe how the proposed Coordinating Center is poised to play a leadership role in the next phase of the NINDS small vessel VCID biomarkers program based on: understanding of and a clear strategy to implement the goals of the Coordinating Center; and a clear structure to advance multi-site VCID biomarkers clinical validation studies including by effective plans for leadership, meeting milestones and other deadlines, and for making meaningful contributions to development, refinement, design and interpretation of appropriately powered multi-site biomarker studies?
Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing biomarker research? Do the investigators demonstrate significant experience with coordinating collaborative basic or clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?
To what degree do the PDs/PIs have proven success and a strong plan for facilitating collaborative interactions, e.g. data requests, harmonization, transfer, sharing of data, samples and protocols, etc., with other investigators and other databases that support research in neurological disorders, including VCID?
To what extent do the Administrative Core and the Data Core each include experienced personnel with a proposed point of contact identified as key personnel for each Core (one each for the Administrative and Data Cores, respectively) with appropriate training and/or experience with both the IT and the biological/clinical data/scientific/project management subject matters that are essential to the success of this consortium?
Does the application propose novel management strategies in coordinating the research consortium the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of management strategies proposed?
To what extent does the application include leading edge and innovative attributes that the proposed Coordinating Center offers the consortium, for example in IT, data management, communication strategies, approaches to organization of meetings and conference calls, and other activities that are the responsibility of the Coordinating Center? Does the application demonstrate expertise in harmonization of data across platforms for metanalyses?
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research consortium the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the consortium, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the consortium is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the consortium? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?
General
How well does the Approach indicate clear administrative commitment and ability, VCID experience including in supporting national consortium-based multi-site VCID biomarkers research or related efforts, and technical ability, to carry out the functions of the Coordinating Center to provide a common support infrastructure that is essential to the goals of the small vessel VCID biomarkers validation consortium? Is the Coordinating Center able to coordinate effectively consortium activities for both fluid-based and imaging-based biomarkers? Is there a clear plan for an efficient transition from the infrastructure of the current NINDS small vessel VCID consortium to the new award?
Has the application documented, including with examples, how the Coordinating Center will provide infrastructure and expertise to drive the consortium administratively and contribute scientifically to validation of biomarkers (applicants are not to propose specific biomarkers or biomarker experiments to be performed during the next five years of this program)?
Administrative Core
Is a clear and effective strategy described for how the Administrative Core will organize, coordinate and administratively drive consortium-specific activities including: committee-related activities; consortium meeting related activities; establishment of a core set of standardized VCID clinical data elements to be used for harmonizing and sharing data; support and advice on informed consent?
Data Core
Is a clear and effective strategy described for how the Data Core will establish infrastructure supporting the required capacity for receiving and distributing data (de-identified clinical data, imaging data, longitudinal data, pathological data when applicable and all relevant control data), a website with public access to basic consortium information and a catalog of data indicating what biosamples are also available, and as well as a consortium-specific portal for data entry and necessary quality control procedures?
Does the application indicate how the Data Core will provide full instructions and support for submitting data in real time, as well as extant data if needed, and for obtaining data from the Core both by consortium members as well as non-members? Is it clear how the Data Core will build into its infrastructure the core set of de-identified clinical data elements agreed upon by the consortium? Does the application detail how the data core will harmonize compatible but not identically coded extant data across platforms for sharing and metanalyses?
Does the application demonstrate a sound plan for quality control and curation of submitted clinical data, and for receiving longitudinal data?
Does the Data Core include statistical expertise that can adequately inform validation study design and analyses?
Milestone Plan
Is the proposed Milestone Plan logical and to what degree does it provide a clear path to successful implementation of the roles of the Coordinating Center?
Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research consortium it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
For research that involves human subjects but does not involve one of the 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.
Not Applicable.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
For Renewals, the committee will consider the progress made in the last funding period.
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.
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 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.
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For consortia 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 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 will receive a written critique.
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.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned on the basis of established PHS referral guidelines 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 (NANDSC). The following will be considered in making funding decisions:
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 recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.6. 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: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
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, Recipients, and Activities, including of note, but not limited to:
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
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.
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.
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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
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, 2 CFR Part 200 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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
The Small Vessel VCID Biomarkers Validation Consortium Coordinating Center PD/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in typical research 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. The NINDS Administrative Project Officer is responsible for evaluating standard budgetary, milestones, and grants and other official reporting to the NINDS. However, the role of NINDS Project Scientists will be to facilitate and not to direct or drive the activities.
The NINDS Project Scientist will:
Areas of Joint Responsibility include:
None
Other Components
External Advisory Committee
The NINDS will establish an independent External Advisory Committee to assist in determining the broad direction of the Consortium.
Milestone Plan
The Milestone Plan, agreed upon by applicant and the NINDS Administrative Project Officer, will be included in the cooperative agreement terms and conditions.
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: (1) a designee of the Advisory Committee chosen without NIH staff voting, (2) one NIH designee, and (3) a third designee with expertise in the relevant area who is chosen by the first two members; in the case of disagreement between the first two members, the third member will be chosen by the Consortium-elected Chair of the Steering Committee. This dispute resolution procedure does not alter the recipient'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, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 – Award Term and Condition 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]
Roderick A. Corriveau, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: [email protected]
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
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 and 2 CFR Part 200.