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.

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

Under the 2009 American Recovery and Reinvestment Act (ARRA), the National Institute of Neurological Disorders and Stroke (NINDS) supported three consortium efforts to develop human induced pluripotent stem cell (iPSC) resources for familial forms of adult-onset neurodegenerative diseases. From this and subsequent efforts, the NINDS Repository now offers 177 human fibroblast lines and 53 human iPSC lines from both healthy control subjects and individuals with Huntington's disease and individuals with familial forms of Amyotrophic Lateral Sclerosis, Frontotemporal Degeneration, and Parkinson's disease. To date the NINDS Repository has distributed over 1000 fibroblast lines and over 400 iPSC lines worldwide to both academic and industry researchers.

Given the rapid advancements in technologies for both iPSC derivation and genome editing, and the continued demand for human fibroblast lines representing both rare and common forms of neurological disorders this funding announcement supports further advancements, expansion, and standardizations in iPSC and fibroblast resources for basic research and drug discovery efforts in neurological disorders supported by the NINDS. It is anticipated that the existing and new resources developed under this FOA will continue to be broadly distributed to both academic and industry researchers worldwide.

Activities required under this FOA include:

• Maintenance and distribution of current fibroblast and iPSC lines available through the NINDS Repository;
• De novo derivation, quality assessment and distribution of new iPSC lines using a standardized non-integrating protocol for derivation. Quality assessment standards should include, but are not limited to those outlined in NOT-NS-14-032;
• Establishment of master and distribution banks for iPSC lines derived by extramurally funded investigators, where the iPSC lines meet banking standards established by NINDS (see NOT-NS-14-032);
• Limited expansion, quality assessment and distribution of fibroblast lines developed by extramural investigators, wherein patient consents allow for banking with a repository and broad distribution of these lines;
• De novo generation, quality assessment and distribution of fibroblast lines from skin biopsies. Quality assessment of fibroblast lines should include karyotyping at the distribution phase to ensure normal karyotypes;
• Generation and maintenance of a peripheral blood mononuclear cell source for future iPSC derivation efforts. Extensive de-identified clinical data must accompany each sample and a global unique identifier (GUID) will be used to link the clinical data with the cell resource;
• Generation, quality assessment and distribution of isogenic iPSC lines through genome editing using standardized protocols. The parent and corresponding genome-edited lines must undergo standardized quality assessments including whole genome sequencing;
• Data management including a catalog of all cell sources available through the NINDS Repository, as well as routine tracking and reporting of submissions, requests, and distribution.

A successful application will have strengths in four major areas of emphasis: 1) iPSC technology and genome editing; 2) project management; 3) resource creation, maintenance, and operation; and 4) data management. Qualifications for applicants should include academic excellence in the field of induced pluripotent stem cell derivation, quality assessment, and genomic editing.

The administrative structure should be such that it provides leadership and program management to the entire project. Because this is a cooperative agreement, extensive collaboration and management input from the NINDS will occur, and milestones will be used to make go/no go funding decisions. This overall structure is intended to insure that stakeholders including academic and industry scientists, and research subjects will be served by the resource. The resource and research activities will also require the continued collection and maintenance of existing NINDS Repository human cell lines and data. Other disorders are likely to be added during the duration of the project. Receipt, processing, storage, and the national and international distribution of iPSC and fibroblast cell lines will be required.

Applications that propose to develop non-human cell resources are non-responsive to this funding announcement.

Due to the unique requirements of this project, applicants are strongly encouraged to consult with NINDS Scientific/Research Staff early on during the planning for an application.

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.

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) 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.

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

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

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

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

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

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).

Applicants must download 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.

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.

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:

Margaret Sutherland, PhD
Telephone: 301-496-5680
Fax: 301-480-1080
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

For this specific FOA, the Research Strategy section is limited to 30 pages.

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.

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

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

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

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

Research Plan:

Acquisition, Characterization, Quality Control and Assurance Measures, De Novo Derivation, Genome Editing, Maintenance and Storage and Distribution for NINDS Repository human induced pluripotent stem cells (iPSCs), human peripheral blood mononuclear cells (PBMCs), and human fibroblasts.

Propose plans that describe how valuable existing and new samples, from projects identified by NINDS, will be supported by the Repository. Plans should address how the proposed procedures and processes will ensure standardized banking and distribution of verified, high-quality, uncontaminated samples that will advance biomedical research. Address each of the following key areas:

• Acquisition. Describe, in general terms, procedures for acquisition of biomaterials and corresponding clinical data for the development of human cell sources including from researchers and clinicians who are not familiar with biomaterial collection for cell source derivation. (Note that cell lines will be identified by NINDS for inclusion after the award is made). Present plans include: 1) the de novo generation of 15-25 iPSC lines per year; 2) the generation of 20-30 fibroblast lines per year, either through de novo establishment from skin biopsies or through limited expansion of NINDS approved lines; and 3) the banking of 40-50 peripheral blood mononuclear cell (PBMC) samples per year. All iPSC, fibroblast and PBMC sources developed through this resource will be approved by the NINDS Scientific Program Director prior to commencement of work.
• It is expected that PBMC samples will be received within 24 hours of each subject visit. Therefore, the Repository must describe an ability to coordinate shipping and to receive samples to accommodate this requirement, including on weekends and holidays if necessary.
• Characterization, quality control and assurance measures. Describe methods for the development, expansion and characterization of a master bank and distribution lot for iPSC and fibroblast cell resources. Describe any sample-specific characterization, and sample-type specific quality assurance procedures planned. Describe genotyping services available for both routine screening of known variants for certain sample types, as well as whole genome sequencing, ancestral informative characterization, or other approaches for genotyping sample collections. For cell lines where genomic modification will be performed, both the parent and modified lines will undergo whole genome sequence characterization. Describe planned sample tracking methods (such as bar-coding or SNP genotyping).
• De novo derivation of iPSC and fibroblast cell sources. Describe strategies to be used for the de novo derivation of iPSC and fibroblast cell resources including the handling and quality assessment of the starting sample types (e.g., skin biopsies, PBMCs, other cell sources). Propose detailed plans for characterization, quality assessment, preparation, storage and distribution of various cell sources. Plans should describe how the proposed methods and processes will ensure the distribution of high-quality, well-characterized samples to the biomedical research community for appropriate uses. Plans should also describe how innovation in derivation methods, sample handling or characterization will be incorporated over the time course of this award. Given the significant variation in expertise at sites that will contribute samples, describe any expectations and training plans for local processing and handling of various sample types at the collection sites.
• Genome Editing. Describe strategies for genome editing that will enable the development of isogenic lines carrying novel mutations or corrections of known mutations. Strategies should include the quality assessment of these lines, including whole genome sequencing of the parent line and corresponding lines that have been genetically modified.
• Maintenance and Storage. Describe plans for maintenance of the existing collection and for re-expansion of samples when needed. Describe safeguards against accidental loss of the collection, including storage of duplicates at a remote site, freezer failure back-up plan, and other contingencies. Describe safeguards to prevent temperature changes when freezers are accessed, alarm systems and procedures, and other safeguards against sample loss. If samples are to be stored under a subcontract, they shall not be distributed or used by the subcontractor without prior NINDS written authorization. Lost samples may be re-collected at the expense of the awardee, at the request of NINDS.
• Additional existing archival sample collections from academics or industry may be submitted to the repository if specific conditions for NINDS approval are met and upon NINDS request.
• Distribution of human iPSC and fibroblast lines. Describe the approach for receiving requests for samples from various requestors, how requests will be acknowledged, how approvals will be sought (if appropriate), and how samples will be distributed. Describe safeguards against any loss or damage to samples during shipping, and strategies to prevent samples not being collected by the recipient upon arrival (to the extent possible). Note: these plans should include both US and international recipients. It is anticipated that world-wide distribution will include 200-300 cell lines per year.
• Describe innovation in cell banking that may accelerate research and standardization of resources through the development and distribution of cell source derivatives such as, but not limited to iPSC-derived neural precursor cell sources. In the description include standardization and quality assessments that will be applied to cell source derivatives to ensure the distribution of a standardized product.

Additionally, applicants should:

• Describe how the details of laboratory standard operating procedures will be shared and publicized.
• Describe your Human Subjects expertise: It is likely that most samples will not be subject to Human Subjects regulations, as most will be de-identified and Health Insurance Portability and Accountability Act (HIPAA) compliant. However, rare collections may have Human Subjects concerns. For this reason, include proposed procedures for evaluating and maintaining adherence to Health and Human Services (HHS) and NIH guidelines and regulations on informed consent and research resources, including information technology security and the implications of the HIPAA regulations Privacy Rule. Describe plans for the Institutional Review Board (IRB) that will review the use of materials that are considered Human Subjects.
• Describe timelines for: processing from sample receipt to storage, sample request to shipping, protocol deviation to reporting to NINDS, and other activities. Where possible, integrate timelines for these activities into project milestones.

Data Repository:

The applicant must describe plans for maintaining a computerized data management system that facilitates retrieval of sample information about NINDS Repository iPSCs, PBMCs and fibroblast cell lines. The plan must present a system that is effective for quality control, tracking of samples, fulfilling orders, billing for cost reimbursement, shipping, and maintaining inventories. Data management plans should also include a back-up system to protect against accidental loss of valuable data. The design and development of the database should be such that it provides a user-friendly accounting of the repository's holdings, and ensures data integrity, accuracy, and security. Such information should include but is not limited to: a global unique identifier (GUID), sample type, links to associated cell resources, de-identified clinical information, a certificate of analysis, including QC data for the lines, cell retrieval and maintenance information, and inventory data. Design of the data structure must allow for easy sharing of the data with other repositories as a means to increase visibility and availability of the cell lines and should include the use of common and disease-specific NINDS common data elements.

Applicants must address their strategy to provide the following:

• A data management plan that includes inventory, catalog, and other necessary information for researchers to access fibroblast, PBMCs and iPSC lines and related de-identified clinical information
• A public web-based interface with the research community to promote the goals of the NINDS Human Cell Resource and Data Repository and to provide tools and information for the collection and use of these cell lines, including ordering samples
• Data management strategies to facilitate easy searching, identification, and requesting of cell lines and their associated data
• Manage data associated with the human cell lines including integration of de-identified clinical data from other data bases or resources

Data management activities must dovetail with a variety of other data management resources in academic and industry settings. Data management capabilities must be: 1) nimble in sharing inventory and catalog data on a regular basis; 2) able to receive de-identified clinical and other sample associated data; 3) able to track and notify (via a message and email system) submitters and requestors; 4) able to incorporate current common and disease-specific NINDS common data elements (CDEs) and 5) able to fully share data with the NINDS Program staff and their designees as appropriate. Dedicated staff with IT and data management experience must be available for trouble-shooting any data management aspects of the project.

Web-based Catalog. Describe plans for a Web-based electronic catalog that lists the available cell lines with associated information about them, including a NINDS global unique identifier, detailed phenotype and molecular genotype data, cell culture history, cell lines and DNA available from family members, pedigree diagrams, and chromosome ideograms, and links to related genetic databases. This catalog will be hosted by the awardee, as well as other databases that increase the visibility of the cell lines available. Catalog information must include a list and explanation of the policies governing the submission and requesting of samples.

Customer Service. Describe plans for customer service, including plans for a user-friendly customer service interface, such as a help-desk. This help-desk function should serve not only IT and data management related concerns, but the entire collection project. For example, this help-desk function would provide support to biomedical researchers who submit samples, submit data, search for samples, have technical questions regarding the submission, or who need assistance with decisions on ordering. The customer service plan must include timelines regarding turn-around time on any query.

Publicizing Repository Collections. Describe plans to publicize repository collections. Efforts may include publishing notices and articles in relevant scientific journals that describe specific repository collections or the general purpose and operation of the repository, presentations at scientific meetings to represent the repository, or other activities. The aim of the activities should be to increase the use of repository collections, to promote awareness of repository services to the scientific community, and/or to aid in recruitment of additional samples for the repository collection when appropriate. These activities must be directed towards scientists and towards the public being served, ie, those with neurological disorders and their friends and families.

Additional Application Elements:

Applicants must also address each of the following key elements:

Milestones. Specific milestones must be presented that will need to be met in order to accomplish the aims. Annual milestones must be provided in the context of a study timeline. These milestones will provide clear indicators of a project's continued success or emergent difficulties. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should include timely processing of sample submissions and requests, and clear communication timelines with NINDS and other stakeholders. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment.

• Describe the research, community(ies) served in terms of providing access to iPSC, fibroblast or PBMC lines, and any unique skills, tools, or experience relevant to the proposed work that are not already detailed in the Biosketch. Describe particular abilities in technology advancements and standardization in iPSC resource development, development and characterization of genetically modified iPSC lines, and iPSC derivatives.
• Cost-Recovery program. Outline an overall cost-recovery program that provides a plan for a charge-back fee for distribution of samples. Ideally, this charge-back plan should take into consideration the importance to the NINDS of serving the community and promoting broad sharing, and therefore, should not be onerous nor provide a disincentive for use of the collection.
• Intellectual Property Rights. Provide a strategy for resource management that addresses the need/requirement for licensing agreements that enable the broad distribution of NINDS repository cell resources to both academic and industry investigators. These licensing agreements should address and provide reasonable solutions for any intellectual property rights that limit the use of the NINDS cell repository cell resources and create egregious demands on the intended cell source recipient or their institution.

Letters of Support: Statements of Institutional Commitment, if appropriate, should be included in this section. In addition, a letter from the applicant should be included and titled "Procedures related to materials obtained from human subjects" that provides documentation of the following:

• That the resource's offices that handle or process the samples and data for biomedical research are in compliance with the Health Insurance Portability and Accountability Act (HIPAA).
• That the resource will not accept specimens for the resource's use from any human subject unless that subject or subject's representative has given signed, explicit consent and the consent follows the language required for broad distribution, banking and utilization as established by NINDS.

All letters of support should be concatenated into one attachment for uploading

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.
• Under this FOA, to ensure the continued availability of resources maintained or developed under this award for the broader research community the resources will remain the property of NINDS.

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

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

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). 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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:
All PD(s)/PI(s) 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 NOT-OD-13-030.

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

For this particular announcement, note the following:

Applications responsive to this FOA support the development, maintenance and distribution of human cell resources including iPSCs, PBMCs and fibroblasts that will play a significant role in advancing basic science and drug discovery efforts for neurological disorders supported by NINDS. Accordingly, since the cell lines developed will be broadly distributed to the research community, reviewers will focus their evaluation on the technology capabilities, quality assurance standards and the level of innovation that will be applied to ensure the research value of this cell resource.

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

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

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

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

Does the applicant/organization have a demonstrated track record in stem cell biology, including in cell source quality control, characterization and distribution?

Does the applicant have experience in data management, including a customer service component?

Does the management plan for the proposed resource support achievement of the proposed goals and milestones?

Does the applicant have a track record which would facilitate understanding and serving the needs of academic communities?

Is there evidence that the investigative team will provide leadership in the field of iPSC resources scientifically?

Does the investigator have experience in genome editing, whole genome sequencing, and generation of stem cell derivatives such as neural precursor cells and differentiated CNS cell populations and characterization?

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?

Is there evidence that new technologies and innovative approaches will be adopted as appropriate to assure high-quality characterization and preparation of cell resources, and to assure that relevant de-identified clinical data and related cell source characterization will be easily accessible by biomedical researchers?

Is there a high likelihood that the activities proposed will be nimble enough to stay current to the greatest extent possible, given rapid advances in iPSC technology, genome editing, and information technologies?

Is there evidence that innovative approaches will be utilized to support the characterization of the sample collection?

Is there evidence of innovative approaches to outreach to the scientific community?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

Are confidentiality and informed consent adequately addressed?

Are the design of quality control, data collection, and analysis appropriate? Does the proposed database provide a user friendly accounting of the resource's holdings and ensure data integrity, accuracy, and security? Is the plan for a back-up facility appropriate? Are plans for customer service likely to facilitate acquisition of cell resources by academic and industry researchers?

Does the application appropriately address evaluation of processes and implementation of improvement plans of the resource's procedures and programs when feedback is given via users or the NIH staff, and is this plan nimble and flexible?

Does the application provide appropriate milestones that will need to be met to accomplish the work set out above in a five-year time frame?

Does the application address a need for broad sharing of protocols and standard operating procedures, and an approach for insuring that these occur?

Does the application give evidence of how protocols will be shared, including via web-based and other methods?

Does the application give examples of how scientific advances will be incorporated into the project?

Does the application provide an adequate strategy to address any intellectual property issues around current technologies used for iPSC derivation and genomic editing and does this strategy minimize the burden to the user of the cell resource?

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?

Has an alternative location been identified for storing duplicate samples in case of natural or other disaster?

Has a plan been delineated in case of equipment or other failure which might jeopardize samples?

Is there adequate server capacity to support a variety of activities including clinical data management, data query, file protocol sharing, genomics and other data banking and management ?

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.

Are plans for publicizing repository collections appropriate and likely to promote awareness of repository collections to the scientific community and/or aid in recruitment of additional cell lines to the repository in a cost-effective manner?

Is the cost recovery plan appropriate for the cell sources provided and in line with other cell source resources?

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

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

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

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

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

Not Applicable

Not Applicable

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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

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

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

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 NINDS National Advisory 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.

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

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

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

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

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

• Planning, organizing, and administering the described work.
• Organizing and chairing Scientific Advisory Committee meetings for the NINDS Cell and Data Repository.
• Participating in NINDS Cell and Data Repository Database Coordinating Committee Meetings to coordinate database information both within and across repositories and other NIH and non-NIH sponsored databases
• Documenting progress in semi-annual written reports to the NINDS Program Director, and providing bi-weekly supplementary status reports.
• Awardees will retain custody of and have primary rights to the software that is developed under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

NINDS will assign a Program staff member to serve as Project Scientist. The Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• Substantial involvement in coordinating the activities of the awardee with other NIH-sponsored biobanks and databases as necessary.
• Participation in NINDS Cell and Data Repository Scientific Advisory Committee meetings.
• Participation in the NINDS Cell and Data Repository Database Coordinating Committee meetings
• Serving as a resource with respect to other ongoing NIH activities that may be relevant to this effort and providing expert advice to the awardee on specific scientific or policy issues.
• Reviewing research resource design and initiatives to ensure that they are within the scope of this effort.
• 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;

Additionally, an NINDS Program Official will be responsible for:

• Normal scientific and programmatic stewardship of the award and will be named in the award notice.
• Monitoring the project on a regular basis. Monitoring may include: regular communication with the PI and awardee staff, periodic site visits or meetings for discussion with the awardee research team, fiscal reviews, and other relevant stewardship matters.
• Formally evaluating the project on a yearly basis. The yearly evaluation will be based on the non-competing application and progress report and recommendations of the NINDS Science Officer.

NINDS reserves the right to terminate or curtail the resource (or an individual component of the resource) in the event of inadequate progress, data reporting, or insufficient use of this resource.

Areas of Joint Responsibility include:

• During the course of the award period, the awardee(s) may be invited to meet with NINDS Project Scientist, and other uninvolved experts in Bethesda, MD, to review scientific progress, the use of the resource, and/or relevant NIH or HHS policies relevant to the resource.
• Existing policies on distribution and appropriate use of repository samples, as outlined in the NINDS Cell and Data Repository Material Transfer Agreement and other established NIH/NINDS policies, will be maintained in the new project period. Changes to existing policies may be developed jointly by the awardee and NINDS staff and must be in compliance with relevant HHS, PHS, and NIH policies.
• The government retains ownership of all cell lines and data associated with the samples in the current repository collection and those developed under this project. NINDS and the awardee will jointly develop a plan to transfer repository cell lines and data to a new repository operator in the event that the awardee does not successfully compete for a subsequent project period.

NINDS Cell and Data Repository Scientific Advisory Committee

The NINDS Cell and Data Repository Scientific Advisory Committee will meet annually to review progress, advancements, innovations and external demand for the NINDS Cell and Data Repository and identify areas within the Cell and Data Repository Program that could benefit from additional reporting, technology development, resources provided or infrastructure.

NINDS Repository Database Coordinating Committee

The NINDS Cell and Data Repository Database Coordinating Committee will meet via teleconference on a monthly basis, or as needed, to coordinate data requirements, form structures, data capture standards and reporting across NINDS repositories, other NINDS or NIH sponsored databases and with additional non-NINDS repository databases.

Opportunities for Partnership

Resource development 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. To ensure that research resources are made accessible to the broader biomedical community, NIH expects applicants who respond to this funding opportunity to submit a plan for: (1) sharing the research resources generated through any grants awarded and (2) addressing how they will exercise intellectual property rights, should any be generated through an award, while making such research resources available to the broader scientific community consistent with this initiative.

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 awardee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special dispute resolution procedure in no way affects the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D and DHHS regulations at 45 CFR Part 16.

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

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

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Margaret Sutherland, Ph.D.
National Institute for 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]

Tijuanna DeCoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
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.