It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance tall 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

Parkinson's disease (PD) is a chronic, progressive movement disorder that affects the lives of at least half a million people in the United States, as well as having significant impact on the relatives and friends who care for them. The average age of onset of characteristic motor symptoms is during the sixth decade, although earlier onset is also possible. Persons with PD also experience significant non-motor symptoms including changes in cognition and mood, sleep disturbances, and autonomic dysfunction. Currently available pharmacological and surgical treatments provide relief from some motor symptoms but fail to attenuate the ultimate progression of the disease. As our population ages, the number of persons with PD is projected to increase significantly.

While considerable research advances continue, the full complexity of PD etiology is not yet evident. Moreover, currently available treatments are primarily symptomatic, and neither slow nor halt disease progression. Challenges posed by the inherent complexity of PD are often best addressed by interdisciplinary research teams working in tandem to surmount obstacles and seize opportunities to advance knowledge and improve treatment. However, development of an effective research consortium, identification of an optimal strategy and collection of rigorous preliminary data to address existing gaps in PD research require dedicated time and resources.

With this initiative, the NINDS is now soliciting Exploratory Grant (P20) applications proposing planning and initiation of synergistic research activities to advance PD research and treatment. The goal of this program is to formalize collaborative structures and establish a rigorous foundation of research discovery necessary to address urgent gaps and emergent issues in PD research. Synergy among proposed research projects must be evident as well as required for successful completion of the overall Exploratory Grant aims. To foster the development of innovative research consortia, this solicitation will provide support to formalize new collaborative directions and/or novel interdisciplinary teams. Successful exploratory studies should lead to a subsequent application for support of a collaborative, interdisciplinary NINDS Morris K. Udall Center of Excellence (P50).

The purpose of this Exploratory Grant (P20) initiative is to support the formation of new collaborative directions and/or novel interdisciplinary research teams to address immediate challenges in PD. Through this mechanism, the NINDS seeks to develop synergistic, proof-of-concept research efforts around investigator-defined gaps in PD research. This mechanism encourages collaborative teams to develop a research plan, construct an effective administrative organization, create standardized policies/procedures, and gather rigorous preliminary data in support of novel ideas to address urgent needs and emergent issues in PD research. The Exploratory Grant theme and proposed research projects will inform the etiology, pathogenesis, or treatment of PD; investigations on related synucleinopathies may be included if such directly address the identified PD research gap. Successful Exploratory Grant activities should lead directly to the submission of an NINDS Morris K. Udall Center of Excellence (P50) application.

The Exploratory Grant provides each individual team with flexibility in project design. For example, some existing teams may have preliminary data for novel projects requiring further proof-of-concept, whereas emergent teams may have identified a key area of need and require time to convene, establish collaborative approaches, and obtain preliminary data. The collective expertise required to form effective partnerships and develop a rigorous evidence base may involve multiple sites and institutions.

Programmatic requirements of this FOA include an Overall section, an Administrative Core, and three or more research feasibility Projects, at least one of which must be led by an early career researcher poised to make contributions to PD research. In this context, "early career researcher" includes those who are about to transition, or have recently moved, to fully independent positions as investigators, faculty members or clinician scientists, and who focus on establishing themselves as experts in their chosen research area. For this initiative, "early career" is inclusive of Early Stage Investigators (ESI), as well junior faculty without current NIH R01-equivalent, independent support; New Investigators are eligible only if the criteria for "early career" are met. Leadership of a research feasibility project will allow ESI to retain ESI status according to NIH ESI policy. Inclusion of an early career researcher is intended to provide a timely leadership development opportunity within the supportive and collaborative structure of the Exploratory Grant consortium.

Because a goal of this initiative is to establish productive and innovative collaborations, extensive preliminary data is not required for proposed research feasibility projects. This FOA is not intended for support of clinical trials, but does permit mechanistic clinical research, as described below. Applicants may also request support for establishment of administrative structures to form the foundation for future basic, translational, and clinical research efforts. Applicants are encouraged to link their proposed theme and activities to critical gaps in PD research, including but not limited to research priorities from the NINDS conference, "Parkinson's Disease 2014: Advancing Research, Improving Lives". Proposed studies must be feasible within the two-year project period and justified within the budget limits described elsewhere in this announcement.

Due to the project timeframe and focus on research feasibility projects, research Cores are not within scope of the Exploratory Grant; applications proposing research Cores will be considered non-responsive to this FOA.

Clinical research is within scope of this initiative but is not required: completion of proposed clinical studies should be feasible within the timeline of the Exploratory Grant. For this solicitation, NINDS will accept hypothesis-driven mechanistic clinical trials in basic and/or translational discovery research in healthy human subjects and in the pathobiology, pathophysiology, and neuropathology of PD. The goal of such studies is to address basic questions and to interrogate concepts in biology, behavior, and pathophysiology that will provide insight into understanding neurological disorders. Such studies may seek to understand a biological or behavioral process, or the mechanism of action of an intervention. Designs that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions must be submitted to an NINDS clinical trial-specific funding announcement (see NINDS Clinical Research). For related information on NINDS policy for submission of clinical trials, see NOT-NS-18-054.

Collection of biospecimens and clinical data will follow policies and procedures of the NINDS Parkinson's Disease Biomarker Program (PDBP).

Per NOT-OD-16-011, the NIH expects applicants to apply rigor in designing and performing scientific research according to the NIH Principles and Guidelines for Reporting Preclinical Research.

This initiative is intended to provide flexibility for new applicant teams to design, establish, and strengthen collaborative efforts, and for existing applicant teams to explore novel research directions. Full-scale multicomponent research projects from established investigative teams, with requirements for supportive research Cores, are best suited to the NINDS Udall Centers of Excellence (P50) program itself.

NINDS funding decisions will focus primarily on scientific merit, i.e., on those applications that are most likely to make innovative contributions to PD research and that demonstrate potential to submit a P50 application at the end of the Exploratory Grant project period. The NINDS will also consider the full scope of Udall Center programmatic activities when making funding decisions; applications proposing goals identical to or largely overlapping with active Udall Centers will receive lower program priority. In addition, the NINDS may also consider whether proposed research addresses recommendations from the NINDS conference "Parkinson's Disease 2014: Advancing Research, Improving Lives."

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

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

Higher Education Institutions

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

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

• 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 - Including the NIH Intramural Program
• U.S. Territory or Possession

Other

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

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

Applicant Organizations

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

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

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

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

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

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

The Exploratory Grant Director (PD/PI) must demonstrate significant potential or proven capacity to provide effective leadership, oversight of administrative activities and coordination of scientific efforts of the Exploratory Grant consortium. Other important considerations include current research productivity and funding, as well as capacity or potential to drive innovative advances as the head of an interdisciplinary team. The PD/PI is responsible for ensuring that consortium goals are met, for developing and managing a decision-making structure, and for allocation of resources to achieve stated goals. The PD/PI must have sufficient research and grant administration experience, including as the PI of R01-equivalent NIH grants or clinical trials, to effectively coordinate this exploratory project. Finally, combined qualifications, expertise and productivity of the PD/PI should support potential for future, successful leadership of an NINDS Udall Center.

PD/PI effort must be commensurate with the time required for effective leadership of the Exploratory Grant.

Current Udall Center Directors, Senior/Key Personnel and/or Other Significant Contributors are not eligible to apply or to participate in P20 applications as Senior/Key Personnel and/or Other Significant Contributors.

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).

Only one Exploratory Grant (P20) will be awarded per applicant organization.

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

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

The letter of intent should be sent to:

Beth-Anne Sieber, PhD
Division of Neuroscience
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: Beth-Anne.Sieber@nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	6
Admin Core	6
Project	6

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative (Admin) Core: required; will include all planning activities
• Projects: required; will include minimum of three research feasibility studies, one of which must be led by an early career researcher

When preparing your application, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

Foreign Justification: If foreign components are included, describe how those present special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and are not readily available in the United States (U.S.) or that augment existing U.S. resources.

Other Attachments: The following information must be uploaded as individual attachments. The filename for each required attachment is indicated below; filenames will be used to bookmark the attachments in the application image.

Organizational Structure: provide a diagram of Exploratory Grant components and related interconnections.

Institutional Resources: Include a description of extant institutional programs, infrastructure, and resources available to advance the Aims of the proposed Exploratory Grant. If applicable, provide a summary of current institutional efforts in PD (or other neurodegeneration or neuroscience) research available to support or complement proposed research efforts.

If applicable, describe existing large-scale research projects at the institution, and define the envisioned contributions of the Exploratory Grant within this context. Examples include, but are not limited to:

• Federal programs: NINDS Parkinson's Disease Biomarkers Program (PDBP); NIH Accelerating Medicines Partnership for PD (AMP PD); NIA Alzheimer's Disease Centers or other significant NINDS/NIA programs in Alzheimer's Disease-Related Dementias (ADRD); Department of Defense Congressionally Directed Medical Research Programs- Parkinson's Research Program (DoD CDMRP-PRP); NCATS Clinical and Translational Science Awards (CTSA).
• Non-Federal programs: Aligning Science Across Parkinson's (ASAP) Research Collaborative Network; Chan-Zuckerberg Initiative (CZI) Neurodegeneration Challenge; Parkinson's Foundation (PF) Research or Clinical Centers of Excellence; large-scale Michael J. Fox Foundation (MJFF) projects and/or consortia; American Parkinson's Disease Association (APDA) Centers for Advanced Research, and similar programs

Enter primary site only.

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

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

The Exploratory Grant Director (PD/PI) must be a recognized leader in scientific research with considerable potential or proven capacity for expert leadership of an interdisciplinary team.

An Associate Director may be named.

The PD/PI is responsible for ensuring Exploratory Grant goals are met, for developing and managing a decision-making structure, and for allocation of resources to achieve stated goals. If named, the Associate Director will partner with the PD/PI to facilitate and advance the goals of the consortium.

The Director and Associate Director (if applicable) will demonstrate current research productivity, active research funding (NIH R01-equivalent or greater) and/or stewardship of clinical studies at time of application submission.

The PD/PI and Associate Director (if applicable) effort must be commensurate with the time required for effective leadership of the Exploratory Grant.

Current Udall Center Directors, Senior/Key Personnel and/or Other Significant Contributors are not eligible to apply or to participate in P20 applications, and therefore may not be named as Senior/Key Personnel and/or Other Significant Contributors.

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

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

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

Specific Aims: All proposed activities will be directed toward the subsequent preparation of a full-scale NINDS Udall Center application. Describe the goals of the collaborative project and outline how the proposed activities will contribute to advancement of these goals and result in the submission of a Udall Center (P50) application.

Research Strategy: The Overall section provides an overview, rationale and timeline for activities leading to the subsequent NINDS Udall Center application. Applicants must identify an over-arching theme that addresses a PD research gap, present a compelling vision and propose a spectrum of activities best suited to their collaborative goals, such as planning meetings, research feasibility studies, and generation of preliminary data.

Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Provide a vision statement for the Exploratory Grant, including expected contributions to the advancement of PD research and treatment. Describe (i) the importance of the PD research challenge or gap to be addressed; (ii) how establishment and/or advancement of the proposed collaboration will improve scientific knowledge, treatment and/or clinical practice; and (iii) the strategy by which the proposed studies will be advanced into an NINDS Udall Center.

Innovation: Provide evidence that the proposed activities will address the stated challenge and advance PD research through use of novel concepts, collaborations, and state-of-the-art approaches.

Approach: Describe the general research framework of the Exploratory Grant. Detail how proposed activities will synergistically address a defined PD research challenge and describe the strategy by which the goals of the collaboration will be met. Clearly state the overarching theme and objectives of the proposed project. For each objective, include a brief statement describing the contributions of individual team members toward completion of common goals. Describe and justify the specific research need to be addressed; when possible, directly relate the theme and objectives to the NINDS PD2014 recommendations. Describe the collaborative planning process, and any related research project(s). Include a narrative timeline or table outlining specific yearly objectives, including transition from planning to implementation phase (i.e. submission of an NINDS Udall Center application).

Describe the leadership structure, the research team, and the role of its members in addressing the stated research challenge and meeting collaborative goals within the two-year timeframe of the Exploratory Grant. To optimize novel team approaches while building upon available knowledge, it is recommended that teams include at least one individual with expertise outside of the PD field and at least one individual with PD expertise, as well as an early career researcher. For members with expertise beyond the PD field, describe how their expertise can be brought to bear to advance project goals and how expected contributions will be integral to consortium activities. Describe the novel contributions of the team to PD research. Provide confirmation of the commitment of team members to partner around common long-term goals to advance PD research.

Provide summary justification for the formation of an Exploratory Grant consortium, including a focus on new collaborative directions and/or novel interdisciplinary teams. Present compelling evidence that the assembled research team will work together effectively to accomplish the goals of the proposed exploratory effort. Detail institutional support for a strong research base on PD and/or other neurodegenerative disorders as well as infrastructure and resources that may be leveraged to support consortium efforts.

Outline envisioned contributions of the proposed activities to the NINDS Udall Centers of Excellence program, including how these contributions will complement (not overlap with) ongoing Udall Center projects.

Letters of Support:

Institutional Commitment (required): Provide endorsement of the planning effort from high-level institutional officials (e.g. Dean, Vice President, Provost; letters from Department Chairs are not sufficient). The letter should include allocation of available resources to PD research and collaborative opportunities with extant institutional programs. Applicant institutions receiving funding from other large-scale, PD-related research projects should detail how interactions with the Exploratory Grant effort will advance PD research and provide a foundational environment for a future NINDS Udall Center application. Outline the role of the institutional official in conflict arbitration and resolution, should such arise among Exploratory Grant investigators.

Collaboration with NIH Intramural Researchers (if applicable): Include a letter from the Scientific Director of the collaborating NIH Institute. The letter must describe the role of intramural staff and specify the nature and amount (funding) of NIH intramural resources to be allocated to the proposed project. In addition, the letter should state that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

Collaboration with Nongovernmental Organizations (if applicable): PD researchers and nongovernmental patient advocacy and funding organizations have common goals for improving treatment and understanding causes of PD. Letters should detail ongoing or planned partnerships between the collaborative team and these organizations.

Letters of support from current Udall Center Directors and investigators are not required.

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.
• The overall Resource Sharing Plan should address plans for sharing data beyond the immediate collaborative Exploratory Grant team.
• Information in the Overall component should complement but not duplicate that provided in Research Project "Resource Sharing Plan."

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Overall)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

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

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

When preparing your application, use Component Type Admin Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

Project Narrative: Do not complete.

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Exploratory Grant Director (PD/PI) must be the Core Lead for the Administrative Core.
• An Associate Director may be named, to assist the PD/PI with oversight of the administrative and scientific efforts of the Exploratory Grant.
• A dedicated Exploratory Grant Administrator must be included.
• The Administrator must be familiar with NIH grants policies and practices and provide effective support to the PD/PI
• Research investigators are not eligible to serve as the Administrator
• Effort of Administrative Core personnel must reflect time required for effective performance of proposed duties

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

Administrative support: Include costs for administrative personnel who will assist the PD/PI with organizational aspects of the project.

Meeting and communications costs: Include costs for travel of project personnel to attend planned in-person meetings of the collaborative team, as well as funds necessary to hold timely web-based meetings.

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

Specific Aims: Describe the function of the Administrative Core in coordination of consortium planning and research activities and as the organizational basis for a future NINDS Udall Center application.

Research Strategy: Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Describe how the Administrative Core will serve as the organizational foundation for planning and research activities of the Exploratory Grant.

Innovation: Describe how the Administrative Core utilizes novel approaches to maximize synergy among investigators to advance the stated goals of the consortium.

Approach: Describe the proposed activities of the Administrative Core including but not limited to the following roles:

• Provide foundational support for the Exploratory Grant Director in consortium oversight and governance.
• Promote the integration and function of Exploratory Grant components, including collaborating institutions, organizational components, investigators, and staff.
• Establish and maintain effective lines of communication.
• Define decision-making processes.
• Develop an evaluation plan for project activities.
• Schedule and organize periodic meetings of consortium investigators.
• Design common protocols and outcome adjudication processes.
• Standardize biospecimen and data collection practices.
• As applicable: Expedite timely transfer of biospecimens to the NINDS BioSEND repository and facilitate timely entry of clinical data into the NINDS Data Management Resource or other NINDS-designated data repository.
• Prepare and submit annual progress reports.
• Provide assurance of compliance with NIH policy requirements.
• Coordinate with the institution(s) and associated regulatory bodies to ensure that human subject and/or vertebrate animal research is compliant with appropriate regulations and guidelines.
• Establish a conflict resolution plan.

Include a detailed timeline of planning activities leading to the submission of a Udall Center application.

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.

As Centers of Excellence, NINDS Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Therefore, Exploratory Grant applicants will detail how the Administrative Core component will coordinate efforts to:

• Facilitate sharing of knowledge, data, research resources and biospecimens with the PD research community as appropriate and consistent with achieving the goals of the program.
• As applicable:
• Expedite timely transfer of information to appropriate, broadly shared databases, including the NINDS Data Management Resource (DMR) or other designated NINDS database, to fulfill data sharing goals as appropriate. Deposition of data solely into an institutional database, whether at the applicant or at a collaborator's institution, is not consistent with achieving the program goals.
• Implement standardized collection and deposition of biospecimens into the designated NINDS biorepository, the Biospecimen Exchange for Neurological Disorders, BioSEND, as well as the NINDS Human Cell and Data Repository (NHCDR), if applicable

Appendix:

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

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Project.

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

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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

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

Project Narrative: Do not complete.

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Research Project investigators (except for the early career researcher(s)) must demonstrate active, R01-equivalent independent funding and/or clinical trial expertise, as well as excellent scientific productivity. As noted for the PD/PI, investigator expertise may also be in areas outside of PD research, if relevant skills can be readily applied to the goals of the collaborative project. At least one investigator leading a project should have proven expertise in PD research. To incorporate new approaches and innovation, it is also recommended that the consortia include and integrate at least one member with expertise from beyond PD research.
• The early career researcher Project Lead will be a promising researcher poised to make contributions to PD research. "Early career researchers" are those who are about to transition, or have recently moved, to fully independent positions as investigators, faculty members or clinician scientists, and who focus on establishing themselves as experts in their chosen research area. For this project, "early career" is inclusive of Early Stage Investigators (ESI), as well junior faculty without current NIH R01-equivalent support; New Investigators are eligible only if the criteria for "early career" are met. Leadership of a research feasibility project will allow ESI to retain ESI status according to NIH ESI policy.
• As applicable: Identify key personnel who will ensure and facilitate data quality, transfer, sharing, and standardized biological specimen collection and submission to the NINDS Data Management Resource (DMR) and NINDS BioSEND repository, respectively.
• Effort of the Research Project Lead and personnel must reflect time required for effective performance of proposed duties.

Current Udall Center Directors, Senior/Key Personnel and/or Other Significant Contributors are not eligible to apply or to participate in P20 research projects, and therefore may not be named as Senior/Key Personnel and/or Other Significant Contributors.

Budget (Research Project)

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

Allocation of budget to research feasibility projects is flexible within the stated budget cap; provide rationale for the specific budgetary needs to meet stated Specific Aims.

Funds cannot be requested for or used to follow extended clinical cohorts or populations, or to collect data and biospecimens beyond those required for research activities of the proposed project.

Biospecimen banking (if applicable): budget for biospecimen collection and banking should be based upon estimates received from the NINDS BioSEND repository, as well as dedication of adequate personnel effort for timely transfer of samples. Quotes are available through the BioSEND Request A Quote website; related questions can be emailed to biosend@iu.edu.

NINDS policy for biospecimen banking requires inclusion of associated costs within application budgets. Investigators are therefore strongly encouraged to contact the BioSEND resource for updated pricing and policies early in the application process, and to include related costs in the Research Project budget.

Collection and transfer of clinical data (if applicable): funds for collection and transfer of clinical data to the NINDS Data Management Resource (DMR) should be included within the Research Project Budget. To harmonize data and foster sharing across PD cohorts, the NINDS expects standardized collection of clinical data.

Induced pluripotent stem cell (IPSC) line derivation (if applicable): applicants proposing to collect human source cells (i.e. fibroblasts and peripheral blood mononuclear cells) for iPSC derivation should include budget and a related quote from the NINDS Human Cell and Data Repository (NHCDR); related questions can be emailed to NINDS@dls.rutgers.edu.

All applicable costs must be anticipated, budgeted, and justified by the applicant; the NINDS will not provide supplemental funds to cover costs for biospecimen and data collection.

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

PHS 398 Research Plan (Research Project)

Specific Aims: Describe hypothesis-driven research activities that will advance the stated goal of the consortium and lead to an NINDS Udall Center application.

Research Strategy: Organize the Research Strategy into sections on Significance, Innovation, and Approach.

Significance: Describe how proposed basic, translational and/or clinical studies will synergize to address the overarching theme of the Exploratory Grant, and how proposed research will advance knowledge of PD. Describe and justify the specific PD research need to be addressed; as applicable describe relevance to the NINDS PD2014 recommendations.

Innovation: Describe novel aspects of the research (e.g. model(s), target(s), method(s), research subjects) and potential to advance state-of-the-art research strategies for PD.

Approach: Describe proposed research feasibility studies. Explain how each proposed research aim relates to the overall theme and priorities of the collaboration and the stated PD research problem. Describe, as appropriate for the nature of the project, experimental methods, and study design, as well as innovation and potential significance to PD research and treatment. Provide justification for and address the validity of proposed PD model systems. If multiple institutions are involved, identify which aspects of the feasibility study will be conducted at which sites. In the absence of preliminary data, provide compelling rationale for the project and the innovative contribution to PD research. Describe the scientific rigor of the experimental design and the strategies used to minimize bias.

Letters of Support:

Utilization of extant biospecimens (if applicable): letters of support or approval for use of those samples, included those banked at BioSEND, must be included. If selected BioSEND samples include those adjudicated by the NINDS PD-Biospecimen Review Access Committee (BRAC), a letter indicating PD-BRAC approval must be included. Approval of sample access requires submission of an online application followed by PD-BRAC review.

Biobanking Quote (if applicable): include a quote from NINDS BioSEND repository for standardized processing and storage of human biospecimens.

NINDS Human Cell and Data Repository (NHCDR; if applicable): applicants proposing to collect human cell sources (i.e. fibroblasts, peripheral blood mononuclear cells) for induced pluripotent stem cell (IPSC) line derivation should include a letter of support from the NHCDR, including detailed plan and timeline for related line development and deposit.

Collaboration with NIH Intramural Researchers (if applicable): Include a letter from the Scientific Director of the collaborating NIH Institute or Center. The letter must describe the role of intramural staff and specify the nature and amount (funding) of NIH intramural resources to be allocated to the proposed project. In addition, the letter should state that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

Collaboration with For-Profit organizations (if applicable): Provide letters detailing planned collaborations with partners, including specific roles of industry and academic investigators. Letters should clearly describe any related intellectual property issues and/or agreements.

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.

As Centers of Excellence, NINDS Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Therefore, Exploratory Grant applicants will detail how each Research Project component will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with the PD research community as appropriate and consistent with achieving the goals of the program.
• As applicable:
• Expedite timely transfer of information to appropriate, broadly shared databases, including the NINDS Data Management Resource (DMR) or other designated NINDS database, to fulfill data sharing goals as appropriate. Deposition of data solely into an institutional database, whether at the applicant or at a collaborator's institution, is not consistent with achieving the program goals.
• Implement standardized collection and deposition of biospecimens into the designated NINDS biorepository, the Biospecimen Exchange for Neurological Disorders, BioSEND, as well as the NINDS Human Cell and Data Repository (NHCDR), if applicable

Appendix:

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

PHS Human Subjects and Clinical Trials Information (Research Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

All human subjects-focused studies in an NINDS Exploratory Grant will employ a common set of tools and resources that will promote the collection of standardized biospecimens and data across sites. Therefore, applicants should comply with related NINDS policies, and relay plans for research standardization of biospecimen collection/distribution/storage, use of Common Data Elements (CDEs) for collection of clinical data, and data collection and storage through the NINDS Data Management Resource (DMR) or another NINDS-designated database. Collection and storage of data solely in an institutional or non-NINDS database fails to meet sharing requirements.

The following information is provided to inform application development as well as prepare successful applicants for subsequent Udall Center program practices.

Global Unique Identifier (GUID)

A Global Unique Identifier (GUID) is required for each Udall Center cohort participant. The NINDS has developed a centralized GUID server for participant sharing across institutes and studies. The GUID allows data to be associated with a research participant without exposing or transferring personally identifiable information (PII) and/or protected health information (PHI). For additional information and to gain access to the NINDS Centralized GUID Server, please contact the NINDS PD Biomarkers Program (PDBP) Operations email: PDBP-OPS@mail.nih.gov.

Standardized Biospecimen Collection and Distribution

Biospecimens obtained from human subjects must be collected using protocols of NINDS BioSEND Biospecimen Collection, Processing and Shipment Manual and related NINDS PDBP protocols.

Biospecimens collected must include whole blood (for DNA and RNA extraction) and serum; collection of peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) is encouraged. Deviation from this plan should be discussed with and approved by the NINDS program officer. Collection of additional biospecimens (e.g. fibroblasts) should be justified within the application and will require NINDS approval.

Informed consent forms must clearly state that any biological samples and de-identified clinical data will be appropriately shared with academics or industry and must be consistent with NINDS BioSEND recommended consent language. A copy of the consent form for each subject should be kept on file by the investigator but does not need to be sent with each sample.

IMPORTANT: costs for biospecimen collection are not included as a component of the NINDS BioSEND repository award. Therefore, most costs for the biospecimen banking are borne by the grantees utilizing this resource (see NOT-NS-15-046). Applicants planning projects in which biospecimens will be collected are strongly advised to consult BioSEND staff to obtain a quote for biospecimen banking costs (email: biosend@iu.edu ).

Similarly, applicants should contact the NINDS Human Cell and Data Repository (NHCDR) for a quote to obtain support for collection of human source cells (fibroblasts, peripheral blood mononuclear cells, PBMC) and derivation of iPSC lines (email: NINDS@dls.rutgers.edu).

Standardized Clinical Instruments

Applicants must collect standard NINDS PDBP clinical instruments (including, but not limited to, demographics, medical history, family history, medications) to maximize data harmonization across PD studies. If additional clinical assessments are proposed, the NINDS strongly encourages researchers to use NINDS Common Data Elements (CDEs), including general and PD-specific CDEs. Exploratory Grant consortia may collect additional clinical information beyond that required by this initiative; those doing so are encouraged to contact the NINDS program official prior to submission. The NINDS PDBP Data Management Resource (details below) has developed web-based forms to streamline data entry and quality assurance.

Clinical Data Management and Storage

Exploratory Grant consortia and NINDS Udall Centers will use the NINDS Data Management Resource (DMR) to store biospecimen-related and clinical data collected. The DMR provides an essential data coordination tool for the entire PD research community through the development of a web-based data management system that provides tools to NINDS-supported projects for both the collection and quality assurance of data in a standardized format. The DMR also coordinates the assembly of de-identified data into a common database thus enabling the query and distribution of aggregate data for the acceleration of PD research. For NINDS Exploratory Grant projects, patient consent must allow broad sharing of de-identified data and biospecimen resources though the NINDS DMR and the NINDS BioSEND and NHCDR, respectively, as appropriate.

Timely deposition of all de-identified clinical data into the NINDS DMR is expected of the Exploratory Grant and Udall Centers program, consistent with program goals. Clinical data submission into the DMR via the Protocol and Forms Research Management System (ProFoRMS) must accompany all biospecimens submitted to the NINDS repository, BioSEND. Submission solely into an institutional or other database does not meet program requirements.

Subject Consent

Informed consent forms for Exploratory Grant clinical studies must clearly state that any biological samples and de-identified clinical data will be appropriately shared with researchers at academic institutions and/or in industry and must be consistent with NINDS BioSEND recommended consent language.

Induced Pluripotent Stem Cells

Proposed derivation of induced pluripotent stem cell (iPSC) lines requires strong justification and will not be supported if proposed studies recapitulate currently available resources, including lines available or pending through the NINDS Human Cell and Data Repository (NHCDR). If derivation of iPSC lines is proposed, the specific research need must be clearly and strongly justified. Applicants proposing to derive isogenic lines should consult the program officer prior to submission. New iPSC lines developed must meet the following criteria: 1) patient consent must allow for broad data and resource sharing (academic and industry investigators) including use for genetic studies, wherein part or all of the genome may be sequenced; 2) associated clinical data must be available; 3) the institution/facility must have licenses for iPSC and related (e.g. genome editing, reporter use) technologies that allow deposition and broad distribution of resulting iPSC lines through the NHCDR; 4) for iPSC lines currently available through the NINDS repository, gene correction experiments must be done in these lines; 5) a timeline must be provided for banking of available iPSC lines at NHCDR; 6) all iPSC lines derived must be characterized for sterility and be free of mycoplasma contamination, have normal karyotypes, normal growth rates and colony morphology, demonstrated pluripotency through a pluritest, scorecard test or equivalent test, demonstrated surface antigen expression of stem cell markers, demonstrated ability to form embryoid bodies and demonstrated transgene silencing for the reprogramming factors used. For gene correction/gene editing projects, investigators will be asked to whole genome sequence the original and edited clones and deposit this data with the NINDS Data Management Resource (DMR) or other NIH-approved repository.

Documentation of the quality assessments, relevant protocols for thawing of cell lines and maintenance of cell lines in culture, passage number and split ratio for each line, information on the method of derivation for iPSC line and any associated licenses with this technology must be provided to NHCDR prior to submission.

Leveraging Existing Research Resources

Applicants are strongly encouraged to include existing research resources for their studies whenever possible. Such resources may include tissue, cellular, or DNA samples from the NINDS BioSEND repository or other existing biospecimen, imaging and data repositories. The NINDS BioSEND repository receives, processes, stores, and distributes biospecimen resources from NINDS funded studies that can be shared by the neuroscience research community, and currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva. Leveraging the resources and support from PD advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged. Studies are also encouraged that leverage the resources of ongoing clinical trials supported through other Federal or private funds.

Applications Involving the NIH Intramural Research Program

NIH intramural researchers may serve as Senior/Key Personnel or Other Significant Contributors on Exploratory Grant research projects. NIH intramural researchers may not serve as PD/PI of the Exploratory Grant.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

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.

The NINDS Udall Centers of Excellence program prioritizes innovative and integrative research with significant potential for discovery. Udall Centers serve as national leaders in and local resources for PD research. The goal of this Exploratory Grant (P20) program is to provide new collaborative teams with the opportunity to plan and obtain preliminary data for a subsequent Udall Center (P50) application.

Accordingly, reviewers will evaluate the significance of the Exploratory Grant theme, the significance and innovation of research proposed, the collaborative potential and skill set of the investigative team, overall synergy of the effort, organizational framework, and the likelihood for success and the potential impact of a subsequent Udall Center award on PD research.

Specific to applications involving clinical trials

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

The scope of this NINDS initiative includes only those applications that propose human mechanistic studies that meet the NIH definition of a clinical trial and that fall within the NINDS research priorities. Therefore, applications may only include hypothesis-driven mechanistic clinical studies designed to elucidate the pathobiology, pathophysiology, and neuropathology of PD and related synucleinopathies. The goal of such studies is to address basic questions and to interrogate concepts in biology, behavior, and pathophysiology that will provide insight into understanding PD. Such studies may seek to understand a biological or behavioral process, or the mechanism of action of an intervention. Such studies are defined as clinical trials but do not seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions.

Accordingly, reviewers will evaluate proposed mechanistic clinical trials within the context of the proposed Udall Center, as well as according to the specific criteria below.

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 Exploratory Grant address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the Exploratory Grant 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?

Is the Exploratory Grant organized around a clearly articulated central theme? Does the proposed project address a defined and timely research challenge in Parkinson's disease? Is the consortium poised to bring new perspective and innovation to PD research?

If successful, will the overall effort establish a "proof of concept" experimental and organizational framework that serves as the basis for a full-scale Udall Center application in two years?

How significant would the reduction in PD disease burden be if subsequent full-scale efforts are successful?

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

Is the PD/PI a productive researcher who is qualified to provide effective leadership, oversight of administrative activities and coordination of scientific efforts of the consortium? Does the PD/PI demonstrate potential or capacity to drive innovative advances as the head of an interdisciplinary team? Is evidence provided that the PD/PI will ensure that consortium goals are met, develop and manage a decision-making structure, and allocate resources to achieve stated goals? Do the stated qualifications of the PD/PI support potential for future leadership of an NINDS Udall Center?

Are the proposed leadership structure and research team optimally poised to address the stated research challenge and meet defined collaborative goals within the timeframe of the exploratory grant?

Is the proposed collaborative team comprised of independent investigators who would be effective project leads in a future, full-scale Udall Center on this topic? Is an early career researcher included as a Project Lead and fully integrated into planned activities? Are the roles of team members clearly defined? Does the proposed consortium represent either a new collaborative effort or new direction for an extant collaborative team?

If the research team includes a member with expertise outside of the PD field, will that expertise advance the stated goals of the project? Is it clear that this investigator's contributions will be an integral aspect of consortium activities?

Is it clear that consortium members are committed to common, long-term goals to advance PD research?

Is the plan for team continuity throughout the exploratory period and into a Udall Center application clear and cohesive?

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?

Will proposed Exploratory Grant activities address the stated challenge and advance PD research through use of novel concepts, collaborations, and state-of-the-art approaches?

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

If the Exploratory Grant involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

If the aims of the Exploratory Grant are successfully completed, will the investigative team have a rigorous evidence base and adequate plan for a subsequent NINDS Udall Center application?

Does the proposed collaborative structure serve as an effective foundation for planning activities and a future Udall Center (P50) application?

Are the proposed studies synergistic and aligned with planning activities of the consortium? Are proposed projects based on sound rationale? Are the proposed experimental models justified? Are the experiments rigorously designed? Is the approach interdisciplinary and likely to advance scientific knowledge, move toward translation of results, and enhance clinical practice for PD?

Is there a timeline detailing yearly objectives and goals, ending with a proposed Udall Center application submission date?

Does justification for the formation of an Exploratory Grant consortium include rationale for new collaborative directions and/or novel interdisciplinary teams? Is compelling evidence provided that the assembled research team will work together effectively to accomplish the goals of the proposed exploratory effort? Is clear indication of institutional support provided, including infrastructure and resources that may be leveraged to support consortium efforts?

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?

Is there evidence of institutional commitment to the goals of the research consortium?

Does the application effectively address how existing resources will be leveraged to advance project goals?

If participating investigators are at different institutions, is a clear plan in place for regular communication and collaboration over the course of the Exploratory Grant?

Significance

Will the Administrative Core serve as the organizational foundation for planning and research activities of the Exploratory Grant?

Investigators

Does the Exploratory Grant Director (PD/PI) lead and dedicate adequate effort to the Administrative Core? Are proposed efforts of the PD/PI, Associate Director (if applicable) and Administrator (required) adequate for effective performance of proposed duties?

If applicable, will the Associate Director provide effective assistance to the PD/PI with oversight of the administrative, planning, and scientific efforts of the Exploratory Grant?

Does the Exploratory Grant Administrator have familiarity with NIH grant policies and procedures, and other skills to provide expert support to the PD/PI?

Innovation

Will the Administrative Core utilize novel approaches to facilitate communication and maximize collaboration among investigators to advance the stated goals of the consortium?

Approach

As proposed, will the Administrative Core provide foundational support for Exploratory Grant collaborative activities and for the Exploratory Grant Director in consortium oversight and governance? Does the Core promote seamless integration and function of Exploratory Grant components, including collaborating institutions, organizational components, investigators, and staff? Does the Core propose to establish lines of communication, define decision-making processes, and develop an evaluation plan for project activities? Will the Core schedule and organize periodic meetings of consortium investigators? Does the Core propose an effective means to design common protocols and outcome adjudication processes?

Is there a clear and actionable plan to standardize biospecimen and data collection practices from the outset? As applicable: is the Core structured to expedite timely transfer of biospecimens to the NINDS BioSEND repository and facilitate timely entry of clinical data into the NINDS Data Management Resource or other NINDS-designated data repository?

Does the Core have the capacity to prepare and submit annual progress reports, provide assurance of compliance with NIH policy requirements and coordinate with the institution(s) and associated regulatory bodies to ensure that human subject and/or vertebrate animal research is in compliance with appropriate regulations and guidelines?

Are effective strategies proposed for conflict resolution, should such arise?

Is there a reasonable timeline detailing yearly objectives and goals, ending with a proposed Udall Center application submission date?

Significance

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

Do the proposed Aims have potential to address the identified PD research gap? Will the proposed Research Project (basic, translational, and/or clinical studies) significantly advance knowledge of PD and serve as the foundation for a competitive Udall Center project?

In addition, for applications involving clinical trials

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

Investigators

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

Is an early career researcher included as a research project lead and well-integrated into the collaborative team? Is the early career researcher sufficiently independent and poised to become an expert in PD research? Excepting the early career researcher, is the Project Lead supported by R01-equivalent independent funding and/or does the Project Lead have significant expertise in clinical trials? Do the investigator's seniority and productivity support strong potential for successful completion of the exploratory grant research project and transition to a Udall Center investigator role? Does at least one research Project Lead have proven expertise in PD research? If the Project Lead has primary expertise outside of the PD field, are her/his skills well-matched to the goals of the project? Does the Project Lead dedicate appropriate effort to achieve the proposed Aims?

If applicable, does the project identify key personnel who will ensure and facilitate data quality, transfer, sharing, and biological specimen submission to the NINDS Data Management Resource (DMR) and BioSEND repository, respectively? If so, do identified personnel have demonstrated expertise in managing data collection/transfer/sharing and standardized collection and submission of biospecimens?

In addition, for applications involving clinical trials

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

Innovation

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

Do novel aspects of the proposed research (e.g. model(s), target(s), method(s), research subjects) represent state-of-the-art research strategies for PD?

In addition, for applications involving clinical trials

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

Approach

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

If the Exploratory Grant involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Do the Aims of the Research Project directly and effectively address the theme of the Exploratory Grant? Will the Research Project synergize effectively with other components to address the overarching theme of the Exploratory Grant?

Is the feasibility of the project supported by either rigorous preliminary data or an adequate, literature-based justification of the identified research gap?

Is the validity of proposed model systems addressed and justified? In the absence of preliminary data, is compelling rationale for the project provided?

Is there strong evidence for scientific rigor as well as inclusion of well-defined strategies to minimize bias within experimental design?

Is the proposed Research Project timeline conducive to that for a subsequent Udall Center application submission?

In addition, for applications involving clinical trials:

Does the application adequately address the following?

Study Design

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

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

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

Data Management and Statistical Analysis

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

Environment

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

Is there evidence of institutional commitment to the goals of the research consortium?

Does the application clearly address how existing resources will be leveraged to advance project goals?

If participating investigators are at different institutions, is there a clear plan in place for regular and effective communication?

In addition, for applications involving clinical trials

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

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

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

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

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

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

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

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

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

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

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

Not applicable.

Not applicable.

Not applicable.

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

Not applicable.

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

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

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

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

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

As part of the scientific peer review, all applications:

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

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke (NANDS) 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.
• Consideration may also include relevance of proposed studies tresearch priorities identified during the NINDS PD2014 strategic planning effort.
• Extent to which proposed efforts are complementary to and non-overlapping with existing Udall Centers.
• Compliance with data and resource sharing policies.

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

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols. Data and Safety

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

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

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights 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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

Beth-Anne Sieber, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Email: Beth-Anne.Sieber@nih.gov

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: NINDSreview@ninds.nih.gov

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS))
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

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

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