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

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

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

Parkinson’s disease (PD) is a chronic, progressive movement disorder that affects the lives of at least half a million people across the United States, as well as having significant impact on the relatives and friends who care for them. The average onset of characteristic motor symptoms, which are initially subtle and increasingly impact purposeful movement, most often occurs in the sixth decade of life; onset at much younger ages 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. While significant research advances have been made, including the identification of environmental and genetic risk factors, a clear cause and a definitive cure for PD have remained elusive. As our population ages, the number of persons with PD is projected to increase significantly.

The NINDS Udall Centers of Excellence for Parkinson s Disease Research program was established in tandem with the Morris K. Udall Parkinson’s Disease Research Act of 1997 (P.L. 105-78), legislation to honor the distinguished Representative from Arizona who lived with PD. NINDS Udall Centers have since identified and characterized disease-associated genes, examined neurobiological and neuropathological mechanisms underlying PD, established improved PD models, developed and tested potential therapeutics, and explored novel avenues of clinical research. In 2020, there are eight Udall Centers across the United States.

The overarching goal of the NINDS Udall Centers of Excellence program is to support specialized research Centers that work collaboratively as well as independently to define the causes of and discover improved treatments for PD. Udall Centers pursue high-impact, synergistic research projects while serving as national leaders in PD research and local resources for research career enhancement and outreach to the PD patient/advocacy community. Another important goal is to further advance PD research through broad sharing of data and research resources developed in this Centers program. The NINDS Udall Centers program prioritizes innovative and integrative research with significant potential for discovery. Udall Center applications are expected to identify, justify, and address an overall research theme that defines a critical challenge in PD research, emphasize novel ideas and approaches, as well as to utilize state-of-the-art technologies and a team-based approach to achieve stated goals. The overall theme of each Center, proposed research projects, and cores will inform the etiology, pathogenesis, or treatment of PD; investigations on related synucleinopathies may be included if such studies directly address the identified PD research challenge.

Each applicant team may submit the combination of research projects (basic, translational, clinical) that best address the stated theme. Basic research has served and will continue to serve as the foundation of discovery in the Udall Centers program: applicants are encouraged to include basic research projects, as well as to continue to build upon this vital foundation with studies that translate basic and clinical research observations into improved treatments for PD. Inclusion of a translational research project is optional but encouraged; such projects should provide initial proof-of-concept that a proposed therapeutic agent has sufficient biological activity to warrant further development for the treatment of PD. Clinical research projects include patient-oriented research with a specific focus on understanding disease mechanisms. When formulating their applications, applicants are encouraged to consider the research recommendations resulting from the NINDS conference, "Parkinson's Disease 2014: Advancing Research Improving Lives."

The Specialized Center (P50) mechanism supports interdisciplinary, hypothesis-driven, synergistic research activities. Required research components of this FOA include: three or more Research Projects, plus a dedicated Udall Catalyst project, 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 PD research. 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 Udall Center program.

Additional required application components include: an Overall section describing the Center theme, vision and organization; an Administrative Core; at least one integrated Research Core that is essential to and accelerates the progress of two or more Research Projects; a mission statement for and description of career enhancement of Center investigators, including the Udall Catalyst project investigator; and a plan for periodic outreach activities to the local patient/advocacy community, including outreach events to convey Center research advances. If at least one Clinical Research Project is proposed, a corresponding Clinical Research Core must also be included within the application. Proposed studies must be feasible within the five-year project period and justified within the budget limits described elsewhere in this announcement.

The following activities are nonresponsive to this FOA; applications containing any of these elements will not be reviewed:

• Pilot research projects.
• Cores that include:
• Research, discovery, or method development.
• Establishment and maintenance of institutional infrastructure and generalized resources (including brain banks, biospecimen repositories, databases, and translational research facilities).
• Deposition of clinical data and/or biospecimens solely in local or institutional databases and/or repositories.
• Recruitment, enrollment, tracking of or collection of data, biospecimens from clinical cohorts beyond that required for proposed Udall Center clinical research studies.
• Activities beyond the scope of defined Udall Center program community outreach activities, including general symposia on PD research and treatment, research-focused symposia for investigators and Continuing Medical Education (CME) programs for health care professionals
• Translational research projects containing:
• Studies of disease mechanism.
• Development of preclinical models for the purpose of understanding disease etiology.
• Target identification, including use of tool compounds.
• IND-enabling studies, such as GLP toxicology, formulation, and manufacturing.
• Discovery and development of therapeutic devices.
• Clinical studies involving non-exempt human subjects research.
• Establishment of institutional infrastructure for therapeutic development activities.
• Clinical research projects containing:
• Clinical trials designed to address safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions.

Responsive applications must demonstrate considerable potential to address critical challenges in PD research; contribute unique knowledge and scientific advances to the Udall Centers program and beyond; collaborate effectively with existing Centers; and serve as national leaders in PD research. Related, supportive factors include, but are not limited to, broad sharing of data and resources as appropriate and consistent with achieving the goals of the program. Udall Centers also serve as local resources for research career enhancement activities for Center investigators, and meaningful outreach activities to the local PD community. Opportunities for collaboration with active NINDS Udall Centers may be considered and included in the application.

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

Applicants proposing to derive and characterize iPSC lines should review NINDS Requirements for Induced Pluripotent Stem Cell Development and Resource Sharing (NOT-NS-14-032) and Notice Announcing the Creation of a Dedicated NINDS Human Cell and Data Repository supporting the Reprogramming, Gene Editing, Banking and Distribution of Fibroblasts and Induced Pluripotent Stem Cells (iPSCs) for Neurological Disorders (NOT-NS-16-003). Applicants are strongly encouraged to use the services of the NINDS Human Cell and Data Repository (NHCDR) for iPSC derivation and genome editing (as well as for fibroblasts and peripheral blood mononuclear cells, PBMC).

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.

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 the potential to collaborate effectively and share broadly across the Centers program and beyond. 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 Udall Center Director (PD/PI) must be a recognized leader in scientific research with proven capacity for visionary leadership of an interdisciplinary team. Other qualifying factors include current research productivity and active research funding (NIH R01-equivalent or greater) and/or stewardship of multi-site clinical studies at time of application submission. To support stated career enhancement goals of the Center, the Director will have demonstrated success in mentoring of junior faculty, postdoctoral fellows, and students. Expertise in areas beyond PD research is encouraged if the Director’s skills can be applied in novel ways to advancement of knowledge of PD causes and progression, with the overall goal of advancing PD research into improved treatments and clinical practice. Center Directors must lead the Administrative Core and may lead no more than one additional component: the PD/PI is expected to commit substantive effort to ensure success of the Udall Center.

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 Specialized Center (P50) will be awarded per applicant organization. i

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	12
Admin Core	12
Core (use for both research and clinical cores)	6
Project (Research and Udall Catalyst)	12

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

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

The application should consist of the following components:

• Overall: required, maximum of 1
• Administrative (Admin) Core: required, maximum of 1
• Research Core: required, minimum of 1
• Clinical Core: required for support of Research Project(s) including Human Subjects
• Projects: categories include Basic, Translational and Clinical
• Research Project: required, minimum of 3
• Udall Catalyst Research Project: required, maximum of 1

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.

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.

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

Institutional PD Research: Provide current institutional framework for PD research available to support or complement proposed Udall Center efforts. Detail how the Udall Center will serve as a nexus for institutional PD research. Include a description of extant institutional programs and resources available to advance the Aims of the proposed Center. Describe existing large-scale research projects, including associated therapeutic development efforts, and define the envisioned contributions of the Udall Center 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.

Foreign Justification: If foreign components are included, describe special resources or characteristics of the research project (e.g., human subjects, animals, disease, equipment, and techniques), including the reasons why the facilities or other aspects of the proposed project are more appropriate than a domestic setting. For example, the justification may include how this component represents special opportunities for furthering proposed Udall Center research through the use of unusual talent, resources, populations, or environmental conditions that are not readily available or that augment existing resources in the United States.

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 Udall Center Director (PD/PI) must be a recognized leader in scientific research with capacity for visionary leadership of an interdisciplinary team.

An Associate Director may be named.

The Director and Associate Director (if applicable) will demonstrate current research productivity, active research funding (NIH R01-equivalent or greater) and/or stewardship of multi-site clinical studies at time of application submission. Additional qualifications include demonstrated experience in mentoring of early career researchers, junior faculty, postdoctoral fellows, and students.

The PD/PI is responsible for ensuring that Center 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 Center.

The PD/PI and Associate Director (if applicable) are expected to commit substantive effort to ensure success of the Udall Center.

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: Provide the overarching research theme and describe the overall aims of the proposed Udall Center.

Research Strategy:

The Overall section states the theme, vision, and rationale for the proposed Udall Center, and provides an overview of planned synergistic activities to achieve stated Aims. Organize the Research Strategy into sections on Significance, Innovation and Approach.

Significance: Provide a vision statement for the Center, including justification for the stated theme, chosen research challenge, scientific premise, and expected contributions to the advancement of PD research and treatment. Include the overall Udall Center program objectives and related implementation plan for the five-year grant period. Justify the proposed interdisciplinary approach and the use of the specialized Center mechanism (P50), including the envisioned contribution as a national leader in and local resource for PD research; related justification may include, but is not limited to, broad sharing of data and research resources consistent with achieving the goals of the program.

Innovation: Describe novel approaches, investigator expertise, and collaborative interdisciplinary activities that will advance the goals of the Udall Centers program, including unique contributions that will elucidate the causes of and result in therapeutic advances for PD.

Approach: Describe the general research framework of the Center. Discuss the proposed research program, highlighting its central theme and define the objectives for the five-year project period. Provide justification for and detail necessity of this specialized Udall Center structure to address the identified PD research gap. Highlight the selected interdisciplinary approaches that will contribute to research advances. Describe the synergy among the Center components, including the Administrative and Research/Clinical Core(s), focusing on the scientific and collaborative approaches that will ensure thematic coherence of Center research and activities. Detailed descriptions of preliminary data for research projects should be included within the relevant Research Project, not in the Overall section. If foreign components are included, describe how those present special opportunities for furthering research programs through unusual talent, resources, populations, or environmental conditions that exist in other countries and are not readily available in the United States (US) or that augment existing US resources.

Provide summary evidence of feasibility for the formation of a Udall Center of Excellence. Present compelling evidence that the assembled research team will work together effectively to accomplish the goals of the proposed Center and advance research in PD. 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 the Udall Center. Describe potential to serve as a national leader in and local resource for PD research. Outline plans for effective sharing of research resources and data with the scientific community.

Letters of Support:

Institutional Commitment (required): Include a letter of endorsement from a high-level institution official(s) (e.g., Dean of the School of Medicine, Vice President for Research, Provost; support from Department Chairs is not sufficient for this purpose). The letter should confirm institutional commitment to the proposed Center, and provide details regarding:

• Intended institutional commitment. Examples of institutional commitment may include but are not limited to: funding for pilot projects; support for recruitment of new scientific talent and career enhancement activities, such as support for a designated Udall Research Fellow; provision of discretionary resources to the Udall Center Director; access to institutional infrastructure; assignment of specialized research space; funding and resources for community outreach activities; and/or other means of support.
• Institutional promotion and maintenance of overall scientific excellence in PD research, including prioritization and integration of the Udall Center into institutional efforts. Udall Centers are encouraged to pursue additional institutional partnership opportunities to further program goals.
• The role of the institutional official in conflict arbitration and resolution, should such arise among Udall Center investigators.
• For applicant institutions receiving funding for other, significant PD-relevant research projects from Federal or Non-Federal entities: describe the unique contributions of the proposed Udall Center to the institutional PD research effort, how interactions among institutional PD-relevant projects will advance PD research and explicate institutional commitment to the support of the Udall Center program in this overall context. Such projects 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: Parkinson's Foundation (PF) Research or Clinical Centers of Excellence; large-scale Michael J. Fox Foundation (MJFF) projects and/or consortia; and American Parkinson's Disease Association (APDA) Centers for Advanced Research.

Collaboration with Nongovernmental Organizations (if applicable): Udall Centers and nongovernmental research, philanthropic and patient advocacy organizations pursue common goals to understand causes of and improve treatments for PD. Include letters from currently collaborating nongovernmental organizations that detail ongoing partnerships with these groups, including support for complementary research activities as well as collaboration on planned Center community outreach efforts such as the research symposium.

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 general plans for sharing data beyond the Udall Center.
• Information in the Overall component should complement but not duplicate that provided for other Udall Center components.

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.

Facilities and Other Resources: Within the description of institutional environment, applicants are required to provide details of proposed Center-specific research career enhancement activities, which address the goals of the Udall Centers program by fostering participating investigator, postdoctoral researcher and student proficiency across the broad spectrum of basic, translational and clinical concepts required to successfully and independently navigate critical issues in PD research.

Capitalizing on the unique interdisciplinary teams within Udall Centers, planned activities will provide opportunities for non-clinician scientists to gain understanding of and exposure to the clinical aspects of PD research, such that basic research is approached as it relates to the clinical manifestation of the disease. Conversely, clinician scientists will gain exposure to and understanding of the basic science that contributes to discovery of disease mechanisms and therapeutic targets.

Career enhancement activities organized by the Udall Center must be separate from institutional training programs and specifically focused on activities that advance investigator skills and knowledge across the Center. This section should specifically detail plans for integration and advancement of the early career researcher for the Udall Catalyst Project. Provide information on the following:

• Mission statement for Center-specific career enhancement activities.
• Brief overview of planned activities over the five-year period.
• Integration of the Udall Catalyst Project investigator into proposed Center activities.
• Strategy for cross-training of basic and clinical Center researchers.
• Complementarity to and collaborations with existing institutional programs.
• Plans for local leadership in and projected outcomes of career enhancement activities for Center students, postdoctoral fellows, and investigators (including the Udall Catalyst Research Project lead).

Active recruitment is not required; rather, the primary goal is to enhance the research career development of young faculty, researchers and students participating in Udall Center projects and cores.

Other Attachments: Provide the following attachment with the filename indicated below (i.e. "Community Outreach Activities"); the filename will be used to bookmark the attachment in the application image.

Community Outreach Activities: The Administrative Core will serve as the point of information for the public, and as the primary Center resource for the local patient/caregiver community.

As Centers of Excellence, the primary goal of Udall Center patient outreach is dissemination of Center research activities within the context of a periodic patient/caregiver community event: outreach activities must be specific to the Udall Center, designed to inform and engage the public regarding Center research advances, as well as how Center research addresses current needs for PD research and treatment. The patient outreach event should be scheduled at least twice, preferably near the beginning (Year 2) and toward the end (Year 5) of the five-year project period.

While these updates may be presented as part of a general outreach event, the agenda must clearly include dedicated presentation of Center research advances; these presentations may be framed to address patient/caregiver interests in research and treatment. General educational updates on PD treatment are not applicable; such can be covered by other departmental, institutional, or nonprofit forum programs. Active participation of patient advocacy groups in the planning and conduct of Udall Center outreach activities, including the research update event, is encouraged.

Research-focused symposia for investigators are not considered patient outreach activities and do not meet the requirement for periodic Udall Center outreach presentations.

Provide a description of planned outreach to the local and national PD patient community, including:

• Plans for periodic Udall Center research outreach presentation, scheduled at a minimum near the beginning and toward the end of the project period.
• Integral involvement of Center investigators and staff in outreach activities.
• Innovative means through which the Center will relay its research advances to the lay community.
• Dissemination of results to Center research study participants.
• Inclusion of a patient advocate on the Udall Center External Advisory Committee (EAC).
• The patient advocate should be named within the application
• To avoid potential conflict of interest, candidates currently participating in a clinical trial at the Center and/or associated medical center should not serve on the Udall Center EAC.
• A lay language summary of Udall Center goals and research activities.
• Broad outreach efforts including Center website, social media approaches.
• Partnership with nongovernmental PD organizations, including patient advocacy groups, research organizations and philanthropic foundations.
• Detail plans for effective outreach to the local patient/advocacy community.

The following activities are beyond the scope of Udall Center-specific community outreach as defined by this FOA: general symposia on PD research and treatment; research-focused symposia for investigators; and Continuing Medical Education (CME) programs for health care professionals.

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 Center Director (PD/PI) must lead the Administrative Core.
• An Associate Center Director may be named to assist the Center Director with oversight of administrative and scientific efforts of the Center.
• A Center Administrator must be named.
• The Administrator must be familiar with NIH grants policies and business practices and provide expert consultation in matters of fiscal administration.
• Research investigators cannot serve as the Center 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.

Budget for the following Udall Center-specific activities should be included in the Administrative Core:

• Annual NINDS Udall Centers Meeting: Include travel and lodging costs for the participating personnel to attend the annual meeting, including but not limited to the Center Director, Center Administrator, and Research Project and Core Leads. The annual meeting is held in the Bethesda, MD area.
• External Advisory Committee (EAC): Include all EAC-related costs in the proposed budget. To promote efficient spending, budgeted costs for EAC member travel will be within range of local per diem rates (as per General Services Administration (GSA) guidance) and follow general NIH guidelines for travel and expense reimbursement rates.
• Udall Center Website: Include all costs for the Center Website.
• Social Media (if applicable): Include costs for development and maintenance of effective Center-based social media outreach strategies.
• Community Outreach Activities: Include funds for periodic community outreach events for the local patient/advocacy community, at which Udall Center investigators relay research ongoing at the Center, as well as funds for other planned Center outreach activities. Budget should be dedicated to presentation of Udall Center activities, rather than for general departmental or institutional outreach. General outreach activities by Udall Center investigators may also be included to provide context for Center-specific plans.
• Career Enhancement Activities: Include funds for general research career enhancement activities for Center students, postdoctoral researchers, and investigators. Administrative Core funds may not be budgeted to fund ongoing institutional programs or for support of individual students, postdoctoral researchers or investigators; associated costs for the latter should be included in the Research Project(s) or Core(s) in which the researchers participate.

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 goals and planned activities of the Administrative Core.

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 research activities of the Center, as well as how it will effectively support Center service as 1) a national leader in and local resource for PD research; 2) a pro-active source for research career enhancement of Udall Center students, fellows and investigators, including the Udall Catalyst investigator; and 3) an effective organizer of periodic, Udall Center-specific outreach activities for the local PD patient/advocacy community.

Innovation: Describe novel approaches utilized by the Administrative Core to maximize synergy among Udall investigators and foster productive relationships with the broader research and patient/advocacy communities.

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

• Promote the integration and function of Center components and activities.
• Provide support for the Center Director in oversight of Center governance.
• Schedule regular meetings of the Center Executive Committee.
• Organize timely meetings of the Center External Advisory Committee (EAC).
• Develop and execute periodic community outreach efforts, including an annual outreach presentation for local PD patients/advocates that focuses specifically on presentation of Udall Center activities and results.
• Coordinate research career enhancement activities within the Center.
• Design common protocols and outcome adjudication processes.
• Standardize biospecimen and data collection practices.
• Expedite timely transfer of biospecimens to the NINDS BioSEND repository.
• Manage deposit of human source cells (fibroblasts, peripheral blood mononuclear cells) and derived induced pluripotent stem cell (IPSC) lines into the NINDS Human Cell and Data Repository.
• Facilitate timely entry of clinical data into the NINDS Data Management Resource or other NINDS-designated data repository.
• Maintain an accounting of resource generation and related utilization, and steps taken to maximize the research utilization of these resources within and beyond the Udall Center.
• Provide advance notice of manuscripts and embargoed publications to the NINDS program official; work with the NINDS Office of Neuroscience Communications and Engagement (ONCE) on press releases and social media outreach highlighting Center accomplishments.
• Prepare and submit annual progress reports.
• Provide assurance of compliance with NIH policy requirements.
• Establish and maintain the Center's website, as well as any proposed social media presence.
• Coordinate Center participation in the annual Udall Centers meeting.

The Approach section should also include plans for the following:

• Administrative Structure: Describe the administrative structure of the Udall Center, including decision-making processes and lines of communication; if applicable, include plans to foster effective communication among investigators at distinct geographic/institutional sites. Detail the administrative, technical, and scientific responsibilities for Center personnel and collaborators.
• Center Governance: Describe plans to convene an internal Executive Committee, consisting of the Center Director, Associate Director (if applicable), Center Administrator, Research Project Leads and Core Leads, to assist the Director with scientific and administrative decisions. Describe Executive Committee activities, including regular meetings to discuss Center activities and direction. Outline inclusion of institutional officials. Include conflict resolution strategy.
• External Advisory Committee (EAC): Provide plans for the EAC, to be composed of at least five outside experts convened to provide unbiased scientific and programmatic evaluation, plus a patient advocate member. Describe the anticipated expertise required on the EAC, but do not name or include letters from potential EAC members. The majority of EAC members should be selected from outside the Udall Centers program and EAC scientific expertise will complement proposed projects. A patient advocate, preferably from the local/regional community, must also be included on the EAC to provide important perspective; the patient advocate should be named within the application. To avoid potential conflict of interest, patients or caregivers participating in clinical trials at the Center and/or associated medical centers should not be selected for the EAC. EAC meetings (in-person or web-based) may be held early, mid-way and toward the end of the project period to obtain timely external assessments of Center progress. The NINDS program officer will attend EAC meetings as an observer and resource for NIH programs and policies. Regular EAC updates and evaluations are to be forwarded to the program officer and included in noncompeting continuation reports during EAC meeting years.

Center Website: Include plans for establishing a Center website. Because the Udall Centers program serves as the nexus of NINDS-funded PD research, members of the research community, advocacy organizations, persons with PD and the public have considerable interest in remaining informed on research progress at each Center. The website should contain a list of research resources as well as a prominently placed, brief (1 paragraph) statement on Public Health Relevance, which describes the goals and recent discoveries of the Center in plain language, as well as how ongoing research may lead to the development of new treatments. Updates should be sufficiently frequent to reflect recent discoveries. The NINDS Udall Centers website provides links to all active Centers.

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants are expected to detail how the Administrative Core component will coordinate Center efforts to:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.
• 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, may not be considered 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 Core.

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

SF424 (R&R) Cover (Research Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Core)

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

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

Project Narrative: Do not complete.

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

List all performance sites that apply to the specific component.

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

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Research Core Lead must have appropriate expertise, as well as a record of productivity and collaboration, to ensure success of the Core. The expertise of the Core Lead may focus in areas other than PD research if relevant skills can be readily applied to the achievement of Center goals.
• Effort of the Research Core Lead and Core personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Research Core)

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

The following parameters apply to Research Core budgets:

Funds to establish or support institutional or general infrastructure (e.g. databases; biospecimen banking efforts, including postmortem tissues) beyond the immediate scope required for Udall Center research activities are not permitted in a Udall Center Research Core. For NINDS policy on support for general banking of postmortem tissue, see: Notice of Change in Funding Mechanism for Brain Banks.

Funds for the following activities should be included in the Clinical Core budget (i.e. not in a Research Core budget):

• Collection of biospecimens from Udall Center cohort subjects enrolled through the Clinical Core.

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 Core)

Specific Aims: Describe the goals and planned activities of the Research Core, as well as the specific means by which it will directly address the overarching theme of the proposed Udall Center. Specify the Research Projects that the Core will support.

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

Significance: Describe the essential relationship of the Research Core to at least two proposed Research Projects, the means through which this Core will advance the aims of each associated project, and specific resources to be generated and shared. Detail how the Core will support the Center's status as a local resource for and national leader in PD research.

Innovation: Describe how inventive use of standardized approaches and Core facilities will: provide essential support for associated research projects; address the overarching theme and enhance synergy of the Udall Center; and contribute to the advancement of PD research.

Approach: Indicate percent usage by proposed Research Projects. Describe how resources generated in Research Cores will be shared within and optimally beyond the Udall Center as consistent with the goals of the program.

Research Core approaches may include, but are not limited to:

• Shared, standardized assays.
• Standardized animal models.
• Omics-based approaches (e.g. genomics, metabolomics, proteomics, transcriptomics).
• Statistics and data management.
• Neuropathology.
• Support for human subjects-based neuropathology is limited to enrolled Udall cohort subjects only, i.e. only those subjects participating in Udall Center clinical research projects (see below).

Research Core approaches cannot include the following:

• Research, discovery, or method development.
• Establishment and maintenance of institutional infrastructure and generalized resources (including brain banks, biospecimen repositories, databases, and translational research facilities).
• Deposition of clinical data and/or biospecimens solely in local or institutional databases and/or repositories.
• Recruitment, enrollment, tracking of or collection of data, biospecimens from clinical cohorts beyond that required for proposed Udall Center clinical research studies.

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants are expected to detail how each Research Core component will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.

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 Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

When preparing your application, use Component Type Core.

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

SF424 (R&R) Cover (Clinical Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Clinical Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Core)

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

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

Project Narrative: Do not complete.

Project /Performance Site Location(s) (Clinical Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Clinical Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The Clinical Core Lead must have appropriate expertise, as well as a record of productivity and collaboration, to ensure success of the Core. The expertise of the Core Lead may be in areas outside of PD research if relevant skills can be readily applied to achievement of Center goals.
• Identify key Clinical Core 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 Clinical Core Lead and personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Clinical Core)

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

Clinical Core funds must be dedicated solely to those clinical research activities necessary to support Udall Center Research Project(s).

Funds cannot be requested or used to follow extended cohorts or populations, or to collect data and biospecimens beyond those required for research activities of the proposed Center. Therefore, funds may be budgeted only for costs associated with subjects who are directly involved in Udall Center research projects.

Specific requirements for Clinical Core budget are as follows:

• Biospecimen collection and banking: The NINDS requires standardized human biospecimen collection protocols and banking at the designated NINDS repository, BioSpecimen Exchange for Neurological Disorders (BioSEND). All studies collecting biospecimens must submit these samples as well as associated clinical data (below).
• NINDS policy requires inclusion of associated costs within application budgets. Investigators are therefore strongly encouraged to contact the following repositories for updated pricing and policies early in the application process, and to include related costs in the Clinical Core budget.
• BioSEND: see the "Request a Quote" page for banking of DNA, RNA, biofluids (blood, serum, plasma, CSF, urine, saliva) and other biospecimens.
• NINDS Human Cell and Data Repository (NHCDR): contact NINDS@dls.rutgers.edu to obtain quotes for: banking of peripheral blood mononuclear cells (PBMC) and/or fibroblasts, induced pluripotent stem cell (iPSC) line derivation and genome editing. All costs for generation of iPSC lines to be developed by the Clinical Core should be included.
• Clinical data standardization and database entry: To harmonize data and foster sharing across PD cohorts, within and beyond the Udall Centers program, the NINDS expects standardized collection of clinical data from Udall Centers. Data are to be collected at least annually for longitudinal Udall Center cohorts, and at baseline (at the least) for familial and genetic cohorts/studies.
• All Udall Center clinical data must be collected using the Protocol and Forms Research Management System (ProFoRMS) module of the NINDS Data Management Resource (DMR), unless otherwise directed and approved by the NINDS Udall Center program officer.
• Applicants must include sufficient, dedicated budget to support timely transfer of data into the DMR or another designated NINDS/NIH database.
• Subject recruitment and retention: Include dedicated budget to support proactive subject recruitment and retention. Recruitment of subjects from diverse populations is an essential element of Udall Center clinical research; allocation of funds for periodic, targeted community outreach programs to increase diversity in Udall Center subject cohorts is strongly encouraged.
• All related costs must be anticipated, budgeted, and justified by the applicant; the NINDS will not provide supplemental funds to cover costs for required 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 (Clinical Core)

Specific Aims: Provide details regarding the subject population to be enrolled, related clinical data and biospecimens to be collected, as well as the specific means by which the Clinical Core will directly address the overarching theme of the proposed Udall Center.

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

Significance: Describe contributions of the Clinical Core to the goals of the Udall Center and its essential relationship to the complementary Clinical Research Project(s). Justify the importance of the patient cohort, and related research, to the goals of the Udall Center program and to the advancement of PD research.

Innovation: Describe how the activities of the Clinical Core, including novel approaches to recruitment and pro-active enhancement of diversity, will address the theme of the Udall Center and advance PD research.

Approach: Describe the proposed activities of the Clinical Core which may include, but are not limited to, the following:

• Recruit, enroll and follow a defined cohort of patients and control subjects to be studied specifically in Udall Center research projects. Provide detailed justification for the cohort, including its size and its direct connection to proposed Udall Center studies, as well as evidence for planned broad consent to facilitate sharing of de-identified clinical data and biospecimens consistent with program goals.
• Utilize and demonstrate compliance with NINDS Parkinson's Disease Biomarkers Program (PDBP) biospecimen collection procedures and required clinical assessment forms.
• If longitudinal analysis of the Udall cohort is planned during the five-year project period, clinical assessments as defined by the PDBP visit schedule must be performed every 12 months, at a minimum.
• If family and/or genetic studies are proposed, baseline clinical assessments (at the least) are required.
• If specific biospecimens or data cannot be collected, please contact the NINDS Udall Centers program officer to discuss alternatives.
• Timely entry of standardized clinical data in the NINDS Data Management Resource (DMR), using the Protocol and Forms Research Management System (ProFORMS) module.
• Standardize collection, submission, and storage of approved biospecimens according to the NINDS Parkinson's Disease Biomarkers Program (PDBP) protocols.
• Deposit approved biospecimens in the designated NINDS repository, including the NINDS Human Biospecimen and Data Repository (BioSpecimen Exchange for Neurological Disorders, BioSEND) and the NINDS Human Cell and Data Repository.
• Provide information and samples to other Centers and researchers as requested. Promote patient education and community outreach, in collaboration with the Administrative Core.
• Integrate new technologies (e.g. mobile technologies, wearable devices, telemedicine) to improve data collection and subject participation.

Applicants should define and specify the Udall Center cohort; cohort recruitment, enrollment and follow-up must be justified by the Aims of the proposed Center research projects. Recruitment, enrollment, tracking of or collection of data, biospecimens from clinical cohorts beyond that required for proposed Udall Center clinical research studies is not responsive to this RFA. If the cohort is followed to autopsy, provide the number of autopsies expected directly through Udall Center studies.

Applicants are strongly encouraged to establish relationships with PD patient and advocacy groups and solicit their input on recruitment and the clinical meaningfulness of the question under study.

Every effort should be made to serve diverse racial and ethnic populations with this Core, especially in areas where those populations represent a significant proportion of the local demographic.

Recruitment and retention plans, including a discussion of the availability of subjects for the proposed study and the ability of enrolling centers to recruit and retain the proposed number of subjects, including women and minorities, should be included. Recruitment and retention strategies should be tailored and targeted for specific populations as appropriate. Strategies should be proven and/or creative/innovative. Data supporting recruitment and retention estimates should be provided. For multi-site studies, a site activation and management plan should be included. Study timeline, including enrollment period, and completion stage, should be feasible within the Udall Center project period.

Collection of biospecimens and clinical data will follow policies and procedures of the NINDS Parkinson's Disease Biomarker Program (PDBP). A Global Unique Identifier (GUID), assigned by the NINDS Data Management Resource (DMR), is required for each enrolled participant. Clinical assessments will include core PDBP clinical elements and will occur at least annually for longitudinal cohorts and at least at baseline for familial cohorts and genetic studies. Collection of clinical assessments beyond the PDBP core assessment should be coordinated with the NINDS. All clinical data will be entered through the Protocol and Forms Research Management (ProFoRMS) module of the NINDS DMR, unless otherwise directed by the NINDS program officer.

To promote broad sharing, collection, and storage of data solely in an institutional or non-NINDS database is not permitted in response to this RFA.

Subject consent is expected to allow for broad data sharing with both industry and academic investigators through the NINDS DMR, as appropriate and consistent with achieving the goals of this program.

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants will detail Clinical Core efforts to:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.
• 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.
• 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.

Deposition of clinical data and/or biospecimens solely in local or institutional databases and/or repositories is not responsive to this FOA.

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.

Informed Consent: provide a draft informed consent form that indicates approval for broad sharing of de-identified clinical data and biospecimens.

Broad sharing of standardized clinical data and biospecimens is crucial for PD research advancement; a related responsibility of Udall Center Clinical Core is to obtain patient consent that allows broad sharing of Center data and biospecimens. For this FOA, subject consents must allow broad sharing of de-identified clinical data through the NINDS Data Management Resource (DMR) and deposition of biospecimens in the NINDS BioSEND repository.

IRB approval of the protocol and informed consent is not required at the time of application submission but is required prior to funding. As such, NINDS encourages investigators to begin these processes as early as possible. Therefore, applicants must provide a draft informed consent form to be used in recruitment and enrollment of Udall Center clinical cohorts, such as that found in recommended consent language from NINDS BioSEND.

PHS Human Subjects and Clinical Trials Information (Clinical Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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.

Basic research projects are hypothesis-driven investigations designed to elucidate disease mechanisms and identify optimal targets for therapeutic intervention. Basic research may utilize model systems or de-identified human biospecimens (see below). While serving as the basis for discovery, this research should be informed and refined by the results of well-designed clinical studies on PD.

For purposes of this FOA, and according to NIH policy, in vitro studies that utilize de-identified human biospecimens (i.e. those falling under 45 CFR part 46.101(b) (4) (Exemption 4)) should be proposed as basic research projects.

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

SF424 (R&R) Cover (Basic 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 (Basic Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Basic 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) (Basic 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 (Basic 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.
• The Basic Research Project Lead must demonstrate excellent scientific productivity and significant potential to advance PD research over the five-year project period. In addition, project leadership requires active, R01-equivalent, independent funding at the time of application submission. The expertise of Project Lead may be in areas outside of PD research if relevant skills can be readily applied to achievement of Center goals.
• Effort of Basic Research Project Lead and personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Basic Research Project)

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

Induced pluripotent stem cell (IPSC) line derivation: projects proposing to develop iPSC lines should include budget for costs related to support from the NINDS Human Cell and Data Repository (NHCDR) in the basic research project, unless those lines will be developed through the clinical core.

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 (Basic Research Project)

Specific Aims: State the aims of the basic research project and the hypotheses to be tested. Justify need for the Udall Center structure to accomplish the proposed aims and highlight synergistic interactions with other Center components.

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

Significance: Describe and justify the identified basic research need in the context of the critical PD research challenge identified by the Center theme. Describe the contributions of the basic research project to achievement of Udall Center goals. Detail how successful completion of the proposed studies will inform and advance PD research and treatment, especially the crucial challenge identified by the Center theme. State the biological rationale for the intended approach, including supporting data from rigorously designed experiments.

Innovation: Provide evidence that use of novel concepts, models, and/or techniques will contribute to the advancement of PD research.

Approach: Describe the experimental approaches and model system(s) utilized to address the specific aims. Examples of basic research projects include, but are not limited to, the following:

• Characterization of cellular and molecular mechanisms of disease processes.
• Elucidation of the mechanism of action, including neural pathways and systems contexts, of identified PD risk genes.
• Identification and characterization of genetic and/or environmental risk factors that predict disease onset and progression.
• Identification of novel therapeutic targets and pathways via hypothesis-driven, mechanistic studies.
• Development of improved animal models, and their use for investigation of disease pathophysiology, progression, and efficacy of therapeutic intervention.
• Research in model systems designed to validate clinically identified biomarkers for disease onset, progression, and response to treatment.
• Use of de-identified human biospecimens, including postmortem tissues and other biospecimens, to elucidate idiopathic or genetic disease mechanisms.

Proposed creation of model systems, including but not limited to animal models and induced pluripotent stem cells (iPSC), requires strong justification and will not be supported if proposed studies recapitulate currently available resources.

Applicants proposing to derive and characterize iPSC lines must comply with NINDS Requirements for Induced Pluripotent Stem Cell Development and Resource Sharing (NOT-NS-14-032) and Notice Announcing the Creation of a Dedicated NINDS Human Cell and Data Repository supporting the Reprogramming, Gene Editing, Banking and Distribution of Fibroblasts and Induced Pluripotent Stem Cells (iPSCs) for Neurological Disorders (NOT-NS-16-003). Applicants are strongly encouraged to use the services of the NINDS Human Cell and Data Repository (NHCDR) for iPSC derivation and genome editing (as well as for fibroblasts and peripheral blood mononuclear cells, PBMC).

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.

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 derivation and deposition. Contact NINDS@dls.rutgers.edu for additional information.

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).

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants are expected to detail how the Basic Research Project will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.

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 (Basic 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

When preparing your application, use Component Type Project.

In general, translational research applies ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease. The specific goal of the Udall Centers translational research project is to accelerate discoveries leading to early human testing of a new drug, biologic, or other therapeutic or preventative intervention for PD. Successful translational research projects will demonstrate that proposed therapeutic agent(s) have sufficient biological activity to warrant further development for the treatment of PD.

Pursuant to the goals of this initiative, Udall Center translational research projects should be directed towards the subsequent pursuit of IND-enabling studies (e.g. through programs sponsored by the NINDS Division of Translational Research, including Cooperative Research to Enable and Advance Translational Enterprises (CREATE) BIO and the NIH Blueprint Neurotherapeutics Network for Small Molecule Development (BPN), and/or by collaboration with industry partners). For example, Udall Center translational research projects could be directed toward the identification of leads (Hit-to-Lead) and optimization of candidate therapeutic leads (Lead Optimization) to move toward future IND-enabling studies or eligibility to enter CREATE and BPN programs at early pre-development stage. Depending upon the scope of the translational research, activities could include demonstration of clear dose-response relationships, in vivo efficacy using clinically relevant outcome measures, in vivo target engagement, in vitro ADME assays, in vitro genotoxicity (Ames test) and cardiotoxicity (hERG activity) assessments, and early in vivo safety read outs (7-day dose range finding in rats). For more examples of complementary drug discovery activities needed to reach IND-enabling studies, refer to BPN PAR-18-546. Only those targeted activities leading to future IND-enabling studies may be included in a translational research project; target identification or mechanistic studies are appropriate for basic research projects only.

Applicants must identify designated translational projects within the application.

Translational Research Projects are focused on use of preclinical model systems. Projects proposing direct involvement of human subjects should be submitted as Clinical Research Projects.

To determine whether a proposed translational research project is responsive to this announcement, applicants are encouraged to contact the Scientific/Research Contact in Section VII, below.

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

SF424 (R&R) Cover (Translational 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 (Translational Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Translational 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.

Other attachments:

Intellectual Property Strategy: Applications are expected to include an Intellectual property (IP) strategy that is no more than one page. Applicants are encouraged to prepare this section of the application in consultation with their institution's technology transfer officials, if applicable.

A goal of this program is to advance research towards the development of products that will benefit the public. Accordingly, applicants should describe the IP landscape surrounding their therapeutic entity. This should include any known constraints that could impede the development of their therapeutic (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program. If the applicant proposes using a technology whose IP is not owned by the applicant's institution, either an investigational therapeutic, FDA-approved therapeutic, or other licensed product, the applicant should address any limitations and move the technology forward consistent with achieving the goals of the program.

If patents pertinent to the therapeutic being developed under this application have been filed, the applicants should indicate the details of filing dates, what types of patents are filed, application status, and associated United States Patent and Trademark Office (USPTO) links, if applicable. Applicants should also discuss future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions.

Project /Performance Site Location(s) (Translational 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 (Translational 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.
• The Translational Research Project Lead must demonstrate excellent scientific productivity and significant potential to advance PD research over the five-year project period. In addition, project leadership requires active, R01-equivalent, independent funding at the time of application submission. The expertise of Project Lead may be in areas outside of PD research if relevant skills can be readily applied to achievement of Center goals.
• Effort of Translational Research Project personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Translational Research Project)

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

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

PHS 398 Research Plan (Translational Research Project)

Specific Aims: State the aims of the translational research project and the therapeutic strategy to be developed. Justify need for the Udall Center structure to accomplish the proposed aims and highlight synergistic interactions with other Center components.

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

Significance: Describe how proposed translational studies will advance development of novel or improved PD therapeutic entities. Detail how proposed studies address the critical challenge identified by the Center theme. State how, if successful, proposed studies will support further development of candidate therapeutics for the treatment of PD, including steps toward IND-enabling research, e.g. via entry into subsequent translational research programs and/or collaborations with industry partners.

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

Approach: Describe proposed therapeutic development activities. Indicate the methodological rigor of proposed studies. Provide the rationale for the chosen model(s) and endpoints, adequacy of controls, route and timing of therapeutic dosing, justification of sample size, statistical methods, blinding methods, strategies for randomization, and robustness and reproducibility of results. Describe how results of the proposed studies will be applied to advance preclinical development, including a plan for continued therapy development that demonstrates an awareness of future goals and challenges. Include preliminary plans to establish the necessary collaborations and funding to further the translational research project.

Responsive translational research studies may include, but are not limited to, the following:

• Target validation, including readouts for target engagement, target activity, and phenotypic results in model biological systems.
• Characterization of candidate therapeutics, including pharmacokinetics, biophysical or physicochemical characteristics, and pharmacodynamic/pharmacokinetic relationship.
• Demonstration of target engagement by the candidate therapeutic.
• Development of pharmacodynamic biomarkers, including those that allow for the direct or downstream readout of target engagement of an intended therapeutic; biomarker studies must comply with policy delineated in NOT-NS-13-020.
• Evaluation of preclinical in vivo efficacy using animal models of PD, particularly in relationship to candidate therapeutic exposure.
• Validation of animal models of PD which include physiologically meaningful endpoints of disease that can be tested in both preclinical and clinical settings.

The following activities are not responsive to this FOA; translational research projects containing any of these elements will not be reviewed:

• Studies of disease mechanism.
• Development of preclinical models for the purpose of understanding disease etiology.
• Target identification, including use of tool compounds.
• IND-enabling studies, such as GLP toxicology, formulation, and manufacturing.
• Discovery and development of therapeutic devices.
• Clinical studies involving non-exempt human subjects research.
• Establishment of institutional infrastructure for therapeutic development activities.

Applicants will leverage existing institutional or collaborative infrastructure for proposed Udall Center preclinical translational projects.

Letters of Support:

Collaboration with Private Entities (if applicable): A letter of support is expected that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) is in place. This letter should come from an official within the private entity who has authority to speak on these issues.

Intellectual Property Management (if applicable): A letter of support is expected from the institutional technology transfer official who will be managing intellectual property associated with this project. If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.

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).

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants will relay how the Translational Research Project will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.

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 (Translational 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

When preparing your application, use Component Type Project.

Udall Center clinical research projects include patient-oriented research, i.e. research that involves direct investigator interaction with human subjects, with a specific focus on understanding the mechanism of human disease.

The NINDS will accept Udall Center applications including clinical studies designed to transiently modify and/or measure a biological process for the purpose of understanding mechanism. These studies are considered clinical trials per NOT-OD-15-015. The NINDS will not consider clinical trials designed to address safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions. Such designs should be submitted to an NINDS clinical trial-specific funding announcement (e.g. PAR-18-420, PAR-18-422).

According to NIH policy, in vitro studies that utilize de-identified samples (i.e. those falling under 45 CFR part 46.101(b) (4) (Exemption 4)) are not considered clinical research. For purposes of this announcement, such studies should be proposed as basic research projects.

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

SF424 (R&R) Cover (Clinical 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 (Clinical Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical 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) (Clinical 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 (Clinical 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.
• The Clinical Research Project Lead must demonstrate excellent scientific productivity and significant potential to advance PD research over the five-year project period. In addition, project leadership requires active, R01-equivalent, independent funding and/or evidence of leadership of a clinical study at the time of application submission. The expertise of the Project Lead may be in areas outside of PD research if relevant skills can be readily applied to achievement of Center goals.
• Effort of Clinical Research Project personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Clinical Research Project)

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

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

PHS 398 Research Plan (Clinical Research Project)

Specific Aims: State the hypothesis and research approaches of the clinical research project. Justify need for the Udall Center structure to accomplish the proposed aims and highlight synergistic interactions with other Center components.

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

Significance: Describe the rationale for proposed clinical studies based on unmet medical need for PD. Describe and clearly justify the identified research need. Address how successful completion of the proposed studies will inform and advance future PD research and clinical trials.

Innovation: Describe novel aspects of clinical studies and potential to inform disease mechanisms and advance state-of-the-art treatment strategies for PD.

Approach: Describe how proposed clinical studies will improve understanding and treatment of PD. State the biological rationale for the intended approach, including supporting data from rigorously designed preclinical experiments and clinical studies. Indicate the methodological rigor of proposed studies. Provide the rationale for the chosen subjects and endpoints, adequacy of controls, justification of sample size, statistical methods, and robustness and reproducibility of results. Areas of investigation may include, but are not limited to, the following examples:

• Improved understanding of prodromal disease and identification of pre-symptomatic PD patients.
• Elucidation of non-motor aspects of Parkinson’s disease, including alterations in mood and cognition, behavioral changes, sleep disturbances, fatigue, autonomic dysfunction, gastrointestinal problems.
• Identification of patient subgroups and at-risk subjects to inform clinical trial design.
• Determination of whether a clinical manipulation produces sufficient evidence of short-term activity, e.g. biomarker activity, target engagement, pharmacokinetic/pharmacodynamic response.
• Development of biomarkers for disease risk, onset, progression, detection, and prevention; biomarkers studies must comply with policy outlined in NOT-NS-13-020.

Proposed Clinical Research projects should have a mechanistic focus, as described above. Completion of proposed research should be feasible within the Udall Center project period.

Letters of Support:

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 HHS regulations for research involving human subjects.

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants will detail means by which the Clinical Research Project will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.
• 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, may not be considered 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.

Eligible data and biospecimens from Udall Center clinical research projects will be shared via the NINDS Data Management Resource (DMR) and NINDS BioSEND repository described in "Other Submission Requirements and Information," below, consistent with achieving the goals of the program. It is expected that all Clinical Research Projects under the Udall Program meet these requirements to promote broad sharing; therefore, informed consent forms must provide related permissions. Informed consent will be obtained through the Clinical Core.

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.

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.

The goal of the Udall Catalyst Research Project is to develop new leadership in PD research by fostering the research efforts of a rising star within the supportive setting of a Udall Center of Excellence. The project may be basic, translational, or clinical, and will follow previously stated guidelines for those project subtypes.

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

SF424 (R&R) Cover (Udall Catalyst 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 (Udall Catalyst Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Udall Catalyst 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) (Udall Catalyst 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 (Udall Catalyst 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.
• The Udall Catalyst Research Project Lead will be a promising early career 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. If an ESI leads the Udall Catalyst project, the individual will retain ESI status according to NIH ESI policy.
• Effort of Udall Catalyst research personnel must be commensurate with the time required for effective performance of proposed duties.

Budget (Udall Catalyst Research Project)

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

The Udall Catalyst project budget should be commensurate with R21 level funding ($125,000 to $150,000 direct costs per year), at a minimum, and sufficient to support proposed research activities across the five-year project period.

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 (Udall Catalyst Research Project)

Specific Aims: State the hypothesis and research approaches of the Udall Catalyst Project. Justify need for the Udall Center structure to accomplish the proposed aims and highlight synergistic interactions with other Center components. Provide information supporting the conceptual and practical independence of the project from that of prior or current mentors. Describe potential for success of the project within the collaborative structure of the Udall Center.

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 with other Center components 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.

Innovation: Provide evidence that use of novel concepts, models, and/or state-of-the-art techniques will contribute to the advancement of PD research.

Approach: Describe the experimental approaches, model system(s) or patient cohort utilized to address the specific aims.

Letters of Support:

Letter of Support, Institutional Official (required): Include a letter from a high-ranking institutional official (e.g. Dean or Provost; not a Department Chair or the Udall Center Director) that confirms the early career status of the investigator and provides supportive information regarding the recent move or pending transition to a fully independent position. Provide additional examples of investigator independence, such as institutional support and available resources, that will foster the establishment of the Udall Catalyst investigator as an expert in PD research.

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 HHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research (if applicable).

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, Udall Centers are expected to share data, resources, and knowledge broadly with the research community. Applicants will detail means by which the Udall Catalyst Project will:

• Facilitate sharing of knowledge, data, research resources and biospecimens with other Udall Centers and the PD research community as appropriate and consistent with achieving the goals of the program.

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.

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 Udall Center will employ a common set of tools and resources that will promote the collection of standardized biospecimens and data within and across participating sites. Therefore, applicants should comply with related policies, and relay plans for research standardization of biospecimen collection/distribution/storage, use of NINDS Common Data Elements (CDE) and NINDS Data Management Resource (DMR) Protocol and Forms Research Management System (ProFoRMS) for standardized collection of clinical data, and data storage in the NINDS DMR or other designated NINDS database. Collection and storage of data solely in an institutional or non-NINDS database fails to meet sharing requirements and is therefore considered non-responsive to this RFA.

• Clinical data and biospecimens are to be collected at least annually for longitudinal Udall Center cohorts, and at baseline (at the least) for familial and genetic cohorts/studies.

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

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 must be collected using protocols of the 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 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 with NINDS Biomarkers Repository 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 will be required to 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. Centers 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 Data Management Resource (details below) has developed web-based forms to streamline data entry and quality assurance.

As appropriate, applicants are encouraged to make use of the following resources for clinical research:

• NIH Toolbox
• Patient-Reported Outcomes Measurement Information System (PROMIS)
• Quality of Life in Neurological Disorders (Neuro-QoL)

Clinical Data Management and Storage

Udall Centers will use the NINDS Data Management Resource (DMR) to store biospecimen-related and clinical data collected for Center projects and cores. 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 Udall Center projects, patient consent should allow broad sharing of de-identified data and biospecimen resources though the NINDS DMR and the NINDS biomarker (BioSEND) and human cell line (NHCDR) repositories, respectively, as consistent with the goals of the program.

Activities that are the sole purview of the DMR include: 1) development of standardized electronic data forms, data formats and software for use across multiple cohorts and projects; 2) development of software to support subject scheduling, site tracking, and facilitation and coordination of de-identified clinical and biospecimen data collection across multiple new and existing cohorts and projects through an easy to use web-based entry system for submitters; 3) quality assurance checks of data entry and collection; 4) development of a user-friendly query system for users to evaluate availability of data and biospecimens within and across Udall Centers; 5) development of aggregate data report formats that are user-friendly and supported by well documented data dictionaries; 6) training for both data submitters and data users; 7) coordination of data and biospecimen summary reports and postings in collaboration with NINDS BioSEND; and 8) public outreach for data submission and data use. Development of all electronic data entry forms and quality assurance checks of de-identified data will be performed by the DMR. Center applications will identify key Clinical Core personnel whose responsibility will be to ensure and facilitate data quality, transfer, sharing, and biological specimen submission to the DMR and NINDS BioSEND, respectively. For those studies already utilizing an institutional data management core or resource, successful implementation of a de-identified data transfer plan from the Udall Center to the DMR will be expected, consistent with achieving the goals of the program.

Timely deposition of all de-identified clinical data into the PDBP DMR is expected of all Udall Centers, consistent with achieving the goals of the program. Clinical data submission into the DMR via ProFoRMS must accompany all biospecimens submitted to the NINDS repository, BioSEND.

Imaging-Based Studies
For applications proposing to include biomedical imaging, including neuroimaging, studies: all formats should be compatible with the Medical Image Processing, Analysis, and Visualization tool (MIPAV).

Subject Consent

Informed consent forms for Udall Center 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.

Studies Ancillary to Parent Studies
Ancillary studies must not interfere with the parent study and must not place undue burden on participants. Approved procedures and policies from the parent study must be followed and must have patient consents that allow broad sharing of de-identified clinical data through the DMR, and deposition of biospecimens in NINDS BioSEND. Review and approval for the use of samples must be completed and a letter of approval must be obtained prior to submission of an application under this RFA.

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.

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.

During the application process, intramural researchers must provide their Scientific Director with copies of formal letters of collaboration, and in turn obtain written approval from the Scientific Director for inclusion within the Udall Center application. All requests for substantial intramural involvement in extramural research activities must also be approved by the Ethics and Grants Management Offices from the respective NIH Institute or Center (IC).

Annual Udall Center Meetings

Annual meetings of NINDS Udall Centers are held each autumn in the Bethesda, MD area. The meeting is designed to provide dedicated time during which Center investigators can discuss emergent issues and approaches in the research and treatment of PD. By providing a focused and interactive agenda, the annual meeting fosters the initiation and continuation of collaborative efforts and resource sharing among the Centers. Meeting planning duties will be shared between the NINDS and the Udall Center Coordinating Committee (UC3).

Udall Center Coordinating Committee (UC3)

The Center Director will participate in activities of the Udall Center Coordinating Committee (UC3), which promotes collaboration and strengthens cooperation among active Udall Centers. For example, the UC3 functions to:

• Strengthen communication and data sharing among Udall Centers.
• Define and share best practices and resources.
• Identify novel collaborative research opportunities.
• Pursue mechanisms for translation of research findings toward clinical realization.
• Coordinate activities in areas of common interest, including investigator career enhancement and community outreach.
• Facilitate interdisciplinary collaboration in PD research among and beyond the Udall Centers.
• Develop, implement, and monitor metrics for the evaluation of program progress.

The UC3 is led by a Chair and an Executive Committee, who work with the NINDS program officer to achieve these goals. The Chair’s term is one year, to start and end at the annual Centers meeting. The UC3 Executive Committee will consist of past, current, and rising Chairs, for a total of three years of service per Chair; respective Center grants must be actively funded during term of service. Each Center Director will be expected to participate on the UC3 for the duration of funding of her/his Center. The UC3 will also include two representatives from Non-Governmental Organizations (NGOs). Additional outside members from the research community will be added on an ad hoc basis to address emergent issues within the program. The UC3 will hold regular teleconferences and will meet annually during the Udall Centers meeting. The NINDS program officer will be included as a participant for all meetings and correspondence.

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, as well as the potential to serve as national leaders in and local resources for PD research.

Accordingly, reviewers will evaluate the significance of the Center theme as well as potential for success based on the collaborative potential and skill set of the investigative team, innovation and impact of research proposed, overall synergy, organizational framework, community outreach, research career enhancement and the potential of the proposed Udall Center to address a critical gap and advance PD research.

In addition, for 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.

Udall Center applicants may propose human mechanistic studies that meet the NIH definition of a clinical trial and that fall within NINDS research priorities. Therefore, applications may 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.

Thus, 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 Center 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 Center 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 Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Does the proposed Center identify and address a critical challenge or gap in PD research? Is there ample evidence that the proposed Center will advance research in PD, through its collaborative team and interdisciplinary projects and cores? Will the proposed Center effectively meet the stated goals of the Udall Centers Program, i.e. to rapidly advance an innovative, interdisciplinary, highly impactful research program while serving as a national leader in and local resource for PD research? Is the use of the Specialized Center (P50) mechanism well-justified, such that the Center structure is essential to address the stated vision, theme and Aims of the application?

In addition, reviewers will evaluate the overarching Significance of the proposed Udall Center:

Do the stated goals of the proposed Center demonstrate the potential for high impact research discoveries leading to advancement in PD research and treatment? Have the investigators successfully conveyed the knowledge and resources to be contributed to the Udall Centers program, and to PD research at the local and national levels?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? 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?

Will the Udall Center Director (PD/PI) provide visionary scientific leadership of the Center? Does the Director have appropriate leadership experience, including leadership of a large-scale research program or clinical study, which predicts success of the Center? Is the Director an established leader in scientific research and/or clinical trials with a history of successful funding? Is the level of effort dedicated by the PD/PI, including leadership of the Administrative Core, well-calibrated to ensure success? If the Director’s primary area of expertise is in an area other than PD research, will the Director’s skills be applied in novel ways to the advancement of PD research and treatment? If proposed, will the Associate Director effectively partner with the PD/PI to facilitate and advance the goals of the Center? Is the level of effort dedicated by the PD/PI and Associate Director (if applicable) adequate to support successful pursuit of Center goals?

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

How adequate are the descriptions of novel approaches, investigator expertise, and collaborative interdisciplinary activities in order to advance the goals of the Udall Centers program, including unique contributions that will elucidate the causes of and result in therapeutic advances for PD

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

Is the Center organized around a clearly articulated central theme? Does that theme address a defined PD research gap or challenge? Is it evident that the specialized Udall Center structure is necessary to effectively address the identified PD research gap? Are the research objectives feasible within the five-year project period? Are identified interdisciplinary approaches likely to contribute to research advances in PD? Is the synergy among the Center components, especially scientific approaches, and collaborative structure, well-described and likely to ensure thematic coherence of Center research and activities? Is there rigorous scientific evidence to support the premise for the proposed Udall Center?

Will successful completion of proposed research objectives directly inform the pathology, progression, and treatment of PD? Is there evidence that individual Center investigators, including the Udall Catalyst project lead, will function as an effective collaborative team to achieve the goals of the Center? Does the proposed Center have the capacity to mobilize institutional resources and contribute to PD research at a local and national level?

Are there appropriate plans for the Center to collaborate and otherwise contribute to the overall Udall Centers program, through participating in collaborative research and sharing efforts, the Udall Centers Coordinating Committee, the annual Center Directors' meeting, and other program-wide activities?

Is standardization of biospecimen and cell line collection/distribution/storage, use of CDEs for collection of clinical data, and data collection and storage through the NINDS DMR or another NINDS-designated database clearly indicated and integral to proposed studies?

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

In addition, reviewers will consider the following:

Will the institution provide support for the Center, e.g. by provision of discretionary resources to the Udall Center Director, recruitment of scientific talent, funding for pilot projects, assignment of specialized research space, access to/use of resources, and/or by any other evident means?

Does the applicant institution support a strong research base on PD and/or other neurodegenerative disorders? If the applicant institution houses other large-scale, PD-related research efforts, is there adequate description of the relationship between the proposed Udall Center and those projects, and is potential overlap addressed appropriately?

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

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? How will the project contribute to the overall success of the Udall Center? Will the proposed research result in substantive rather than incremental advances in PD research?

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 mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

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

If the project lead does not have current NIH funding, does (s)he have active, independent funding that is the equivalent of an NIH R01 or demonstrated stewardship of a multi-site clinical trial? Is investigator effort adequate to advance research project and Center activities?

Is an early career researcher leading the Udall Catalyst Project? Is strong justification provided regarding the early career researcher, including sufficient independence and readiness to develop into an expert in PD research? Is there evidence that the Udall Catalyst lead will be fully integrated into the synergistic activities of the proposed Udall Center, including career enhancement activities?

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, or technologies? Are the concepts, approaches or methodologies, or technologies novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or technologies proposed?

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

Does the project address the overall Center theme, and is it highly synergistic with other proposed projects? Are the objectives of the proposed project defined and feasible within the five-year project period?

For the Udall Catalyst Project, does proposed research synergize with the Overall Center theme? Is there evidence of seamless integration into the collaborative structure of the Center? Are resources provided sufficient to ensure successful completion of the project as proposed?

If proposed, is the basic research project appropriately designed to elucidate disease mechanisms and/or identify optimal targets for future therapeutic intervention? Are proposed model systems likely to address the stated hypothesis? Is the premise informed by clinical PD research and/or grounded in foundational research approaches? If the project proposes to develop novel model systems, is related justification provided, including novelty and lack of overlap with available models?

If proposed, does the translational project have the potential to lead to the development of a novel or improved therapy? Is the study appropriately structured to demonstrate whether proposed therapeutic agent(s) will have sufficient biological activity to warrant further development? Is the proposed model, including timing of treatment and route of delivery, justified and are appropriate endpoints included? Is the intellectual property landscape clearly described and justified? Will successful completion of proposed studies lead to further IND-enabling research, either via entry into translational programs and/or industry partnerships? Are the applicants aware of goals and challenges, as well as necessary collaborative interactions required, for future therapy development?

If proposed, is the rationale for the clinical research project founded upon a rigorous body of high quality preclinical or clinical research? Are the conceptual or clinical framework, designed, methods and analyses adequately developed, well-integrated, well-reasoned and appropriate to the aims of the project? Are the subject population and stated endpoints well-justified?

In addition, for applications involving clinical trials:

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 and rigorous 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 measure(s), 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 biological or behavioral 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? 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 quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

In addition, for applications 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?

Reviewers will provide overall numeric scores for the individual cores based on criteria below.

Administrative Core

Does the Administrative Core Lead/Center Director have appropriate expertise and dedicate adequate time to administrative activities and overall Center coordination? If an Associate Director is named, does that person have expertise to effectively assist the Center Director with scientific and administrative management of the Center? Does the Center Administrator have documented expertise with NIH policies, practices, and fiscal management to provide support for the program?

Is the line of communication clear between the Center Director, Associate Director (if applicable) and Center Administrator? Does the Core provide a suitable plan for establishing and maintaining effective communications and cooperation among Center investigators and with investigators outside the Center? Is the proposed management structure appropriate for scientific administration, coordination of resource generation and utilization, as well as fiscal administration, procurement, property, and personnel management, planning and budgeting? Does the Core support the Center's role as a national leader in PD research?

As structured, will the proposed internal Executive Committee provide the Director with timely, expert assistance regarding Center scientific and administrative decisions? Are regular meetings proposed? Are institutional officials effectively integrated into structure and communication flow of the Executive Committee? Is the proposed conflict resolution strategy well-reasoned and feasible?

Are there appropriate plans and timeline for establishing the External Advisory Committee (EAC)? As proposed, will the expertise of the EAC effectively contribute to the oversight of Center research projects, and other components? Are planned meeting intervals conducive for timely input? Is the EAC patient advocate member identified? Is the EAC role of the advocate delineated?

Are proposed internal and external procedures for monitoring and evaluating the proposed research projects and core facilities/resources stated? Are there coherent plans for management of data, animal models and other resources?

Does the Facilities and Resources section of the Administrative Core clearly describe research career enhancement activities, including a mission statement for and overview of planned activities, and are those activities appropriate for the specific scope of the proposed Center? Are proposed activities well-integrated into the theme of the Center? Are career enhancement activities specifically designed for Udall Center investigators, i.e. are activities separate from and do they enhance/build upon existing institutional resources and programs?

Are proposed Center outreach activities sufficiently periodic, i.e. occurring at least twice during the project period? Is the outreach designed specifically to inform and engage the public regarding Udall Center research, as well as how that research integrates into current advances in PD research and treatment? Do Center investigators participate in community outreach efforts to increase awareness and convey the importance and implications of their research activities to the patient and advocacy communities? Does the Community Outreach attachment outline a clear and appropriate strategy for the organization of a periodic, dedicated Udall Center community outreach event, at which specific Udall Center research advances will be conveyed? Are plans establish a Center website provided and effective? If social media outreach is proposed, are related plans clear, timely and well-justified?

Research Core

Is the Research Core essential to advance the scientific aims of at least two proposed research projects? Does the Core address the central theme and enhance the synergy of the overall program? Will the facilities or services provided by the Core (including procedures, techniques, and quality control) be used effectively? Are the Core Lead and key personnel well-qualified to provide the Core service(s), and is adequate effort dedicated? Does the Core demonstrate potential to generate and share resources that support the Center's status as a local resource for and national leader in PD research? As designed, will the activities of the Core likely contribute to the advancement of PD research?

Clinical Core

Is the Clinical Core essential for the support of the proposed clinical research project(s)? Does the Core Leader have the appropriate expertise, seniority, and dedicated effort to direct the proposed Clinical Core facility? Are qualified clinical core personnel identified to cover all functions of the Core (e.g. subject recruitment/enrollment, data and biospecimen collection and handling)? Are there appropriate plans for the rigorous management and quality control of any research data or materials to be obtained from human subjects?

Is the proposed cohort specifically defined and justified by the Aims of proposed Center clinical research projects? Is there evidence of nonspecific enrollment and follow-up unrelated to Udall Center research projects? Have specific numbers for expected autopsies been provided and justified?

Are plans in place for subject recruitment? Is there a specific and feasible plan for inclusion of diversity in subject recruitment, and is planned enrollment appropriately reflective of the local demographic? Is the proposed subject cohort well-defined and appropriately diverse? Are proposed plans for recruitment and retention of the population innovative? Is planned enrollment justified and required by proposed Center clinical research project(s)? Is the timeline for the clinical cohort accurate and feasible within the project period?

Have standard operating procedures been established for collection and storage of biological samples and/or for genotype/phenotype information? For longitudinal cohorts: will annual biospecimen collection adhere to protocols of the NINDS BioSEND repository, and is timely deposition of biospecimens into the NINDS BioSEND repository addressed? Will clinical data collection occur annually, using standardized NINDS PDBP clinical assessments? Do plans include standardized collection and timely transmission of data to the designated NINDS Data Management Resource (DMR)? If the cohort is familial or genetic, is timely deposition of baseline data and biospecimens planned? Will any additional clinical information be collected using NINDS Common Data Elements (CDEs)? In general, is there a clear and cohesive plan to deposit clinical data and biospecimens from the defined Udall Center cohort in the NINDS-designated database (DMR) and biorepository (BioSEND)?

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 Center 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 Center 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.
• Proposed research is complementary to/non-overlapping with existing Udall Centers.
• Compliance with NINDS and NIH data and resource sharing policies.
• Consideration of NINDS programmatic priorities may also include relevance of proposed studies to research priorities identified during the NINDS PD2014 strategic planning effort.

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.

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).

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: 301-637-3015

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)
Telephone: 301-496-5680
Email: Beth-Anne.Sieber@nih.gov

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: nindsreview@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.