NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted.

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 one million people across the United States, a figure that is expected to increase as our population ages. The average onset of characteristic motor symptoms, which are initially subtle and increasingly impact purposeful movement, occurs in the sixth decade of life; onset at much younger ages is also possible. PD is a complex condition which also includes significant non-motor symptoms such as 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 possible environmental and genetic risk factors, a clear cause and a definitive cure for PD have remained elusive.

As the primary Federal funder of PD research, the National Institute of Neurological Disorders and Stroke (NINDS) supports a significant investigator-initiated PD research portfolio as well as several targeted efforts. One of these programs, the NINDS Udall Centers of Excellence for Parkinson’s Disease Research , was established in tandem with passage of the Morris K. Udall Parkinson’s Disease Research Act of 1997 (PL 105-78). The objective of the NINDS Udall Centers (P50) program is to establish a network of Centers that work independently as well as collaboratively to define the causes of and discover improved treatments for PD while serving as local resources for and national leaders in PD research. Current Udall Centers focus on hypothesis-driven approaches to elucidate the neurobiological mechanisms of disease onset and progression, building upon the considerable strengths of the Udall Director and investigators who are most often based at a single or few academic institutions in the United States (US). While this model represents one effective means to advance knowledge of underlying causes of and potential treatment for neurological disease, surmounting persistent obstacles requires transformative efforts of large, specialized (and often international) research consortia using a unique combination of knowledge, skills, innovation, cutting-edge technologies and resources in a goal-driven approach to resolve an essential research priority. With this P20 initiative, the NINDS is now soliciting applications for exploratory activities leading to an entirely new and focused Center without Walls (CWOW) approach, designed to enable the formation of novel, highly skilled and synergistic international collaborations that harness emergent technologies to define and resolve a critical problem in Parkinson's disease research within a 5-year period.

Purpose

The purpose of this FOA for Exploratory Grant (P20) applications is to support the formation of new, highly skilled research consortia to address urgent and emergent challenges posed by the inherent complexity of PD. Challenges to understanding, treating and curing PD exist at every level of the research enterprise: basic (e.g. the structure and transmission of toxic species of a-synuclein, molecular links between risk genes and neurobiological pathways and circuits), translational (e.g. development of disease-modifying therapies and biomarkers; predictive disease models) and clinical (e.g. individual differences in PD manifestation and course; treatment of symptoms that are resistant to dopamine replacement therapy). Moreover, elucidation of key interrelationships among these research areas requires deeper investigation and skillful collaboration; for example, an understanding of synuclein structure would facilitate development of an imaging ligand that could be utilized to track disease progression and response to treatment; development of a valid preclinical model would both contribute to understanding of neurobiology and improve therapeutic development; understanding individual differences in PD, including the contribution and penetrance of genetic risk, would result in a personalized approach to treatment. Resolution of particularly difficult challenges therefore requires a collaborative, transdisciplinary approach on a different scale: a "Center without Walls (CWOW)" approach, in which a specialized research consortium works seamlessly across institutional, geographic and research boundaries using a goal-driven approach to resolve an essential question or controversy in PD.

Development of an effective research consortium, identification of an optimal strategy and planning of comprehensive efforts to address fundamental challenges in PD research require dedicated time and resources. Therefore, this NINDS initiative will provide up to two years of support for new collaborative teams to initiate planning, develop organizational structure, perform research feasibility studies and obtain preliminary data that will lead directly to the submission of a competitive NINDS Morris K. Udall Center without Walls for PD Research (Udall PD CWOW) application. The Exploratory Grant mechanism provides each applicant consortium with flexibility in choice of PD research challenge and project design. That stated, the consortium will select and justify a timely, relatively implementation-ready challenge, such that the team can effectively mobilize required data, skills and resources within a two-year period. Because a goal of this initiative is to establish new research consortia, preliminary data is not required for proposed research feasibility projects. The components required to form effective partnerships and develop a rigorous evidence base will involve a range of research expertise, emergent technologies, multiple geographically distinct sites and institutional resources. All activities will be directed toward development and submission of a subsequent NINDS Udall PD CWOW application. Udall PD CWOW applications are expected to transform PD research and treatment through transdisciplinary, synergistic and timely resolution of an identified critical challenge in PD research. The anticipated scope of ensuing Udall PD CWOW applications (Section IV. Application and Submission Information, Part 7. Other Submission Requirements and Information, below) will include the optimal combination of preclinical and clinical research, plus the optimal technological skills and resources, necessary to address the identified challenge and to meet stated goals within a five-year project period. A P20 Exploratory Grant Award is not a prerequisite for submission of a Udall PD CWOW U54 application.

Exploratory Grant Scope

Responsive applications will define an essential PD research priority with transformative potential and demonstrate the ability to meet timelines for planning activities, as well as considerable potential to: rapidly convene a new, highly skilled, and facile research consortium; contribute unique knowledge and scientific advances; provide broad sharing of data and resources consistent with achieving the goals of the cohesive NINDS Udall Centers program; and develop goals for a subsequent Udall PD CWOW application that will resolve the defined, essential challenge in PD research within a five year period using a goal-driven approach.

To foster the rapid development of dynamic research consortia tailored to meet essential challenges, this FOA will only support new collaborations among world-class researchers; continuation of established projects and teams will not be supported. Therefore, to be considered "new," the consortium must represent a novel collaboration among independent investigators who have not co-authored primary research publications within the past two years. The consortium must also include transdisciplinary expertise as demonstrated by primary training, professional affiliation and research expertise of its members. Consortium novelty is also defined by the combination of research methodologies, expertise and significance of the challenge selected.

The following activities are within the scope of this FOA:

• Selection and justification of an essential PD research priority, resolution of which requires a transdisciplinary, goal-driven, consortium-based approach.
• Development and coordination of the research consortium.
• Establishment of administrative and governance structure, including an internal Executive Committee.
• Organization of planning meetings (face to face, web-based, teleconferences) to:
• Convene the consortium
• Meet timelines of the Exploratory Grant effort
• Finalize goals and a transdisciplinary, thematically integrated, synergistic strategy to meet the identified research challenge.
• Develop a strategic plan for an NINDS Udall PD CWOW application, including an initial milestone draft.
• Prepare the Udall PD CWOW application.
• Pursuit of research feasibility projects, including exploratory mechanistic clinical trials (defined below).
• Organization of existing tools for research management and broad sharing of data consistent with achieving the goals of the program.
• Coordination of standardized procedures for collection and storage of data and biospecimens according to NINDS and NIH policies.
• Leveraging institutional and existing resources to achieve exploratory goals.

The following activities are beyond the scope of this FOA:

• Continuation of ongoing, or recapitulation of prior, collaborative research efforts.
• Incremental expansion of knowledge, data, resources or technologies.
• Advanced therapeutic development.
• Interventional clinical trials.
• Research Cores.
• Consortium efforts housed at less than three geographically distinct institutions.
• Establishment of institutional research infrastructure and/or research resources (e.g. cell repositories, brain/tissue/biospecimen banks, data bases/repositories, etc).
• Career development/research training activities.
• Outreach and education.

Applicants will provide justification for larger-scale, goal-driven efforts required to resolve the identified challenge within a subsequent five-year NINDS PD CWOW period. The Udall PD CWOW is expected to include larger-scale research collaborations, in terms of numbers of investigators, research projects and dedicated resources, than current NINDS multicomponent grant mechanisms including the NINDS Research Program Project Grant (P01) mechanism or the NINDS Udall Centers of Excellence (P50) Program. Full-scale multicomponent research projects from established investigative teams at a single or few institutions, with requirements for supportive research Cores, are best suited to the NINDS Research Program Project Grant (P01) mechanism or the NINDS Udall Centers of Excellence (P50) Program itself (the latter if clinical populations, community outreach and career enhancement activities are included, in service of status as a local resource for and national leader in PD research). Support for research cores and resource establishment (e.g. research infrastructure, biospecimen repositories, databases) is beyond the scope of this FOA; cores will be required in the subsequent CWOW approach. Support for the development of research resources, including but not limited to preclinical animal models and induced pluripotent stem cells, are best pursued through alternative mechanisms described on the NINDS Grants Mechanisms website. Biomarkers studies may be best supported through NINDS PD Biomarkers Program (PDBP) and Neuroscience Biomarker Program initiatives. Support for interventional clinical trials, also beyond the scope of this P20 mechanism (see Applicable Clinical Research Studies, below), is available through funding opportunities described on the NINDS Clinical Research website. Support for advanced therapeutic development activities is also out of scope; related funding opportunities are listed on the NINDS Translational Research website.

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.

Program Considerations

NINDS funding decisions will focus primarily on scientific merit, i.e., on those consortia that are best poised to develop a competitive Udall PD CWOW application and resolve an essential challenge in PD research within a subsequent five-year project period. Key considerations include the transformative significance of the defined challenge, the novelty and skillset of the research consortium, and the potential for rapid, innovative solution of the proposed problem. The NINDS will also consider the full scope of ongoing activities in PD, including active Udall Centers and other existing Federal and non-Federal research consortia (e.g. NINDS PD Biomarkers Program (PDBP), NIH Accelerating Medicines Partnership for PD (AMP PD), Parkinson's Progression Markers Initiative (PPMI)) when making funding decisions; applications proposing goals identical to or largely overlapping with ongoing activities will receive lower program priority. In addition, the NINDS will consider the degree to which proposed activities justify and address an essential challenge in PD research, including but not limited to specific research priorities identified during the NINDS conference "Parkinson's Disease 2014: Advancing Research, Improving Lives."

Applicable Clinical Research Studies

Clinical research is within scope of this initiative but is not required proposed clinical studies should be designed in accordance with the exploratory nature and feasible within the timeline of this initiative. For this FOA, NINDS will accept applications that propose human mechanistic trials/feasibility studies that meet NIH's definition of a clinical trial and that fall within the NINDS research priorities. NIH defines a clinical trial as A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes (NOT-OD-15-015)." NIH also defines exploratory mechanistic studies in human subjects as clinical trials; such studies are "designed to explore or understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention. These studies may focus on basic and/or translational discovery research in healthy human subjects and in human subjects who are affected by the pathophysiology of diseases and disorders (NOT-OD-18-010).

NINDS supports hypothesis-driven mechanistic clinical studies in basic and/or translational discovery research in healthy human subjects and in the pathobiology, pathophysiology, and neuropathology of neurological disorders. The goal of such studies is to address basic questions and to interrogate concepts in biology, behavior, and pathophysiology that will provide insight into understanding neurological disorders. Such studies may seek to understand a biological or behavioral process, or the mechanism of action of an intervention. Designs that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions must be submitted to an NINDS clinical trial-specific funding announcement (see NINDS Clinical Research). For related information on NINDS clinical trial policies, see NOT-NS-18-011 and NOT-NS-18-054.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

The Exploratory Grant Director (PD/PI) must be an established leader in scientific research with proven stewardship of successful large-scale research consortia, eminently qualified to provide visionary leadership of a Udall PD CWOW as well as effective oversight of CWOW administrative activities. Leadership of the Udall PD CWOW will require coordination with existing governmental and non-governmental efforts in PD research, as well as the utilization of available resources and infrastructure to advance the goals of the Center.

Other important PD/PI qualifications include but are not limited to: outstanding productivity; current research funding (NIH R01 equivalent or greater for preclinical researchers) and/or stewardship of a large, multi-site clinical study (for clinical researchers); and proven success in the effective leadership of innovative transdisciplinary team efforts. The PD/PI is responsible for ensuring that consortium goals are met, for developing and managing a decision-making structure, and for allocation of resources to meet stated goals. Expertise in other neurodegenerative diseases and disciplines is encouraged if the Director’s skills can be applied in novel ways to resolution of the chosen PD challenge. The PD/PI must be located at an institution in the United States (U.S.). PD/PI effort must be commensurate with effective leadership of an intensive period of P20 exploratory research and planning activities. The PD/PI would be expected to commit substantive effort to a Udall PD CWOW application.

Directors of active, large-scale research efforts, including NIH multi-component grants (e.g. NINDS Udall Center, P50; NIA Alzheimer's Disease Research Core Center, P30; NIH Program Project Grant, P01), are eligible to apply as PD/PI. However, the proposed planning efforts must be novel, in terms of investigative team and science, and non-overlapping with ongoing research efforts.

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).

A button to access the online ASSIST system 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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.

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

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

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

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

The letter of intent should be sent to:

Beth-Anne Sieber, PhD

Division of Neuroscience

National Institute of Neurological Disorders and Stroke (NINDS)

Telephone: 301-496-5680

Email: sieberb@ninds.nih.gov

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	6
Project (use for Research Feasibility Projects	6

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

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

The application should consist of the following components:

Overall: required

Administrative Core: required; will include all proposed planning activities

Project: required; will include a minimum of three research feasibility studies.

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

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

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

Exploratory Grant Organizational Structure: Provide a diagram illustrating interaction among Exploratory Grant components and institutions.

Exploratory Grant Timeline: Provide a timeline (in table, flow chart or chronological narrative format) for consortium activities, including:

• Initiation: convening consortium
• Exploration: research feasibility projects
• Evaluation and Priority Setting: consortium decisions shaping implementation
• Implementation: Udall PD CWOW application

Describe the roles of the investigators and research sites in achieving timeline goals.

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 PD/PI must be an established investigator with expertise in the successful stewardship of large-scale preclinical and/or clinical research programs, eminently qualified to provide effective oversight of administrative activities and leadership of scientific efforts of the consortium. Other important considerations include current research funding and/or stewardship of a large clinical trial, documented and current research productivity, and capacity for effective leadership of an innovative, transdisciplinary research consortium. Expertise in areas outside of PD research is encouraged if the PD/PI's knowledge can provide novel insight into the defined PD challenge. The PD/PI is responsible for ensuring that consortium goals are met, for developing and managing a decision-making structure, and for allocation of resources to meet stated goals.

An Associate Director with similar qualifications may be named; the primary role of the Associate Director will be to assist the PD/PI with coordination of research planning efforts.

Exploratory Grant key personnel must be established investigators who are optimally qualified to provide effective leadership of future scientific projects or research cores within the consortium. Other important considerations include current research funding (NIH R01 equivalent or greater for PhD researchers; stewardship of clinical studies for MD researchers) and excellent productivity, as well as successful participation in collaborative research efforts (e.g. leadership of large-scale clinical research efforts for MD clinicians). In addition, key personnel must have the seniority and skills required for effective project leadership in the subsequent Udall PD CWOW application. The expertise of key personnel may focus in areas other than PD research if relevant skills can be readily applied to the objectives of the Exploratory Grant and achievement of future Udall PD CWOW goals. Investigators will closely coordinate activities with the PD/PI to meet exploratory grant timelines and targets.

To optimize novel team approaches and perspectives in addressing critical challenges, overall consortium key personnel must include at least one individual with complementary and/or applicable expertise outside of the PD field and be anchored by at least one individual with PD expertise. Inclusion of international collaborators with critical expertise for reaching proposed goals is encouraged. These inclusions are intended to enrich the perspectives and methodologies brought to bear on resolution of key issues in PD research. All key personnel must dedicate appropriate effort to pursuit of Exploratory Grant activities.

Key personnel will also include an Exploratory Grant Project Administrator. The Project Administrator must be proficient in NIH grant policies and business practices and provide consultation in matters of fiscal administration; consortium investigators should not assume this role. The Administrator will work closely with the PD/PI on overall implementation of planning activities, participate in Internal Advisory Committee activities, and communicate with consortium members.

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:

Clearly state the objectives of the proposed exploratory effort, including the essential PD challenge to be addressed initially herein and subsequently by the ensuing Udall PD CWOW application. Describe the goals of the transdisciplinary consortium. Justify the goals within the framework of relative readiness for implementation. Detail organizational and research activities directed toward the subsequent preparation of a full-scale NINDS Udall PD CWOW application.

Research Strategy:

Propose a compelling vision, strategic approach and a spectrum of organizational and exploratory research activities best suited to the stated consortium goals. Synergy must be evident among consortium sites and research feasibility projects such that successful completion of the Overall aims could not be accomplished without the consortium framework.

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

Significance: Provide a vision statement for the Exploratory Grant, including how the effort will (i) enable pursuit of a fundamental PD research priority; (ii) build an exemplary collaborative team; (iii) gather supportive preliminary data and (iv) demonstrate exceptional potential to pursue a targeted, thematically integrated strategy to remove a critical impediment blocking advancement of the understanding and treatment of PD. Describe the means by which planning efforts establish a "proof of concept" conceptual, organizational and research framework that will serve as the robust foundation for a full-scale Udall PD CWOW application.

Innovation: Provide evidence that the proposed activities will advance PD research through use of novel concepts, collaborations, and approaches. Highlight unique skillsets and novel resources that will be brought to bear by participating investigators and sites. Provide evidence that the proposed planning activities will address the stated challenge through dynamic use of collaborative approaches and resource sharing among participating sites. Detail novel means proposed to facilitate consortium communication during the planning process.

Approach:

• Overview: The Research Strategy should describe the methods, techniques, and analyses that the Exploratory Grant will employ to achieve the vision laid out in the Overall aims. Applicants should provide a general discussion of: 1) the significance of each individual feasibility project and how each contributes to the overall consortium goal; 2) the overall strategy of the Administrative core for managing the center and ensuring that all goals are completed in a timely fashion; 3) innovations in techniques and methods that will contribute to accomplishing the research goals and meeting the defined PD challenge; and 4) how each site and each investigator is uniquely positioned to contribute world-class expertise and cutting-edge resources towards resolving the identified challenge.
• PD Challenge: Define the essential PD challenge to be addressed by the Exploratory Grant; when relevant, directly relate the theme and objectives to the NINDS PD2014 research priorities. Directly relate Exploratory Grant objectives to the stated research challenge. Justify the significance and timeliness of the challenge using literature citations, data from other sources, or when possible, from investigator-generated data; preliminary data is not required. Detail how proposed activities will synergistically and dynamically address an essential PD research challenge and describe the strategy by which the goals of the consortium will be met. For each objective, include a brief statement describing the contributions of individual team members toward completion of common goals. Describe the collaborative planning process and related research feasibility projects. Describe the dynamic transition from consortium initiation to implementation phase (i.e. submission of an NINDS Udall PD CWOW application) based on the implementation-readiness of the chosen PD research challenge.
• Research Consortium: Describe the research consortium, leadership structure and the role of its members in addressing the stated research challenge and meeting collaborative planning goals. Detail the administrative, technical, and scientific responsibilities for Exploratory Grant key personnel. Describe the novel contributions of the team to PD research, including any unconventional or emergent approaches that may be utilized to resolve the selected PD challenge; for members with outside expertise, describe how their contributions will be brought to bear to advance consortium goals. Provide confirmation of investigator commitment to partner around cohesive, long-term PD research goals. Provide a plan for team continuity throughout the planning period and PD CWOW activities. Detail how geographically separate investigators will be aligned into a cohesive planning approach. Detail relevant collaborative connections among planning sites and other entities such as nongovernmental organizations and industry. To optimize novel team approaches while building upon available knowledge, teams will include at least one individual with expertise outside of the PD field and at least one individual with PD expertise. For members with expertise beyond the PD field, describe how their research and/or technical expertise can be brought to bear to advance project goals. Provide a plan for team continuity and for conflict resolution.
• Exploratory Grant Research Approaches and Goals: Detail the degree of synergy among research projects and sites; provide justification such that successful completion of the aims could not be accomplished without the consortium structure. Highlight relative contribution of resources and services to the goals of planning efforts as well as a following Udall PD CWOW application; include a description of how existing tools will be leveraged for research management and broad sharing of data and resources, consistent with achieving the goals of the program. Outline envisioned contributions of the proposed activities to the NINDS Udall Centers program, including how these contributions will complement (not overlap with) ongoing Udall Centers.

Letters of Support:

Institutional Commitment, Applicant and Participating Institutions (required): Provide endorsement from appropriate high level institutional officials (e.g., Dean of the School of Medicine, Vice President for Research) at the application and consortium sites, including allocation of available resources to PD research and a delineation of how this Exploratory Grant effort will provide a strong foundation for a subsequent NINDS Udall PD CWOW application.

The letter should provide details regarding:

• Institutional promotion and maintenance of overall scientific excellence in PD research, including prioritization and integration of the Exploratory Grant into institutional efforts. Consortia are encouraged to leverage additional institutional partnership opportunities and available resources to further program goals.
• The role of the institutional official in conflict arbitration and resolution, should such arise among Udall PD CWOW investigators.
• For applicant and participating institutions receiving funding for other, significant PD-relevant research projects from Federal or Non-Federal entities: describe the unique contributions of the Exploratory Grant 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 Exploratory Grant 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) 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.

Institutional Partnerships (if applicable): Applicants are encouraged to leverage institutional partnerships, programs and resources to further Exploratory (and future Udall PD CWOW) goals. Provide letters from institutional partners; such partners may include large-scale research efforts mentioned above as well as resource cores and additional programs that may advance planning goals.

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 consortium. 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). Additional information is available in Part 2. Section IV.7, below.

Collaboration with Non-Federal Entities (if applicable): PD researchers share common goals (e.g. for understanding etiology and improving treatment) with nongovernmental, philanthropic and international research organizations, as well as with the biotechnology and pharmaceutical sectors. Letters should detail planned partnerships between the consortium and these groups, including the allocation of related knowledge, data or resources.

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.

Rapid, organized and broad resource sharing are consistent with the goals of the NINDS Udall Centers program. Therefore, the overall Resource Sharing Plan should address plans for data and resource sharing beyond the immediate collaborative Exploratory Grant team.

Information in the Overall component should complement but not duplicate that provided in Research Project Resource Sharing Plans.

Appendix:

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 NIH-defined human subjects research, clinical research, and/or 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

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. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

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

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

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

Budget for the following Exploratory Grant activities should be included in the Administrative Core:

• Administrative support: salary support required to enable effective planning leadership by the PD/PI, the Administrator, and essential key personnel at the applicant institution.
• Travel: Include costs for travel for project personnel to attend planned meetings of the consortium.
• Meeting support: Audiovisual and technical equipment rental and related support, rental costs for conference space and supplies needed for conduct of the meeting.

To promote efficient spending, budgeted costs for consortium 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.

The following budget requests are out of scope:

• Funds for transportation costs exceeding US carrier coach class fares.
• Funds for food and beverages.
• Funds for planning meetings held at non-US sites.

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 role of the Administrative Core in coordination of consortium planning and research activities and as the organizational basis for a future NINDS Udall PD CWOW application.

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

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

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

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

• Provide support for the PD/PI in oversight of consortium governance and communication.
• Promote the integration and function of consortium components and activities.
• Monitor and maintain the timeline for consortium activities.
• Coordinate regular meetings of the consortium participants, including the initial consortium meeting to be held within two months of award.
• Organize periodic meetings of the internal Executive Committee.
• Design common protocols and outcome adjudication processes.
• Standardize biospecimen and data collection practices.
• Expedite timely transfer of biospecimens to the NINDS BioSEND repository.
• Facilitate timely entry of clinical data into the NINDS Data Management Resource or other NINDS-designated data repository.
• Assure compliance with NIH policy requirements research at all sites.
• Oversee protection of data confidentiality and intellectual property (if applicable).
• Establish consortium policies for data sharing and publication.
• Maintain an accounting of resource generation and steps taken to maximize the research utilization of these resources by the consortium.

The Approach section should also include plans for the following:

• Planning Activities: Provide a timeline for planning meetings and teleconferences. Provide details regarding location and structure of the initial planning meeting, which should be held within 2 months of award. Provide information on frequency of teleconferences and/or web meetings to maintain consortium communication. Detail approaches, including available information technologies (e.g. web-based sharing, data portals) that will be used to facilitate communication and coordination among investigators across geographic locations. Provide a proposed date, location and structure for a meeting to conclude planning via development of final milestones, preparation and submission of an NINDS Udall PD CWOW application.
• Administrative Structure and Governance: Describe the administrative structure for the Exploratory Grant, including lines of communication, decision-making processes, and procedures for resolving conflicts. Describe plans to convene an internal Executive Committee, consisting of the Director (PD/PI), Associate Director (if applicable), project Administrator, and feasibility Research Project Leads PIs, to assist the Director with scientific and administrative decisions. The Executive Committee may include a community stakeholder (person with Parkinson's or caregiver) with relevant interest and expertise in consortium objectives; to avoid potential conflicts of interest, such participants should not be enrolled in a clinical trial at any of the consortium sites. Describe Executive Committee activities, including regular meetings to discuss consortium activities and direction. Describe inclusion of institutional officials in consortium planning and implementation, including role in resolution of potential conflicts. Important note: External governance structure should not be implemented for the Exploratory Grant. An external Steering Committee will be required for Udall PD CWOW governance and should be assembled only after award of a successful U54 application, in collaboration with NINDS program staff.
• Standardized Biospecimen and Data Collection Procedures: Acknowledge and include plans to use standardized procedures for collection of biospecimens and clinical data, described in "NINDS Research Standardization Practices" in Part 2, Section IV.7.

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.

Rapid, organized and broad resource sharing are consistent with the goals of the NINDS Udall Centers program. Therefore, the Resource Sharing Plan should address the role of the Administrative Core in data and resource sharing during and beyond the proposed collaborative Exploratory Grant period.

Applicants are expected to detail how this component will:

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

Appendix:

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 (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or 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

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

When preparing your application in ASSIST, use Component Type Project

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. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

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.

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Research Project investigators must demonstrate world-class expertise and exemplary productivity in the proposed research area. In addition, investigators much have active, R01-equivalent independent funding and/or experience with leadership of multi-site clinical studies. Teams must be anchored by at least one PD researcher. To maximize potential for new insights and incorporation of cutting-edge approaches, consortia will actively integrate at least one investigator with primary expertise in another, complementary research area whose skills can be readily applied to the goals of the collaborative feasibility project.
• NIH Intramural researchers may serve as project investigators; a Letter of Support from the Scientific Director of the associated NIH Institute/Center (IC) is required (see below).
• Identify key personnel who will ensure and facilitate data quality, transfer, sharing, and biological specimen submission to the PDBP DMR and NINDS Repository, respectively.
• Effort of Research Project personnel must be commensurate with the time required for effective performance of duties.

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

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

The following budget considerations apply to projects proposing to collect clinical data and biospecimens:

• 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: contact NINDS@dls.rutgers.edu to obtain quotes for: banking of peripheral blood mononuclear cells (PBMC) and/or fibroblasts, iPSC generation and genome editing.
• 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 a Udall PD CWOW. Data are to be collected at least annually for longitudinal cohorts, and at baseline (at the least) for familial and genetic cohorts/studies.
• All Exploratory Grant clinical data must be collected using the Protocol and Forms Research Management (ProFoRMS) module of the NINDS Data Management Resource (DMR), unless otherwise directed by the Udall Center program officer. Applicants must include sufficient dedicated budget to support timely transfer of data into the DMR or other designated NINDS 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 clinical research.

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 activities.

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.

While preliminary data is not required, applicants should provide sufficient evidence of feasibility to support proposed studies. Specific studies must be described; open-ended requests for pilot funds are not responsive to this announcement. The goal of this Exploratory Grant program is to identify an essential challenge, convene a dynamic consortium and implement goal-driven resolution of that challenge in an NINDS Udall PD CWOW application. Therefore, requested support for the creation of model systems, including but not limited to animal models and induced pluripotent stem cells (iPSC), requires strong justification and will not be provided if proposed studies recapitulate currently available resources; for specific information on iPSC, please see Section IV. Application and Submission Information, Part 7. Other Submission Requirements and Information, below. Applications proposing to recruit clinical cohorts must justify the need for that cohort to address the PD research challenge, both in the Exploratory Grant and Udall PD CWOW phases of challenge resolution.

Specific Aims: Describe proposed research activities that will advance the stated goal of the consortium and lead to an NINDS Udall PD CWOW application. State the hypothesis of the proposed feasibility research project and include techniques and methodologies that will be utilized.

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

Significance: Describe how proposed studies will address the central PD research challenge of the Exploratory Grant, and the potentially transformative nature of challenge resolution.

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

Approach: Describe proposed research feasibility studies. Explain how each proposed research aim relates to the overall priorities of the consortium and the stated research challenge. Describe, as appropriate for the nature of the project, experimental methods and study design, as well as potential to advance PD research and treatment. Provide justification for and address the validity, as applicable of proposed PD preclinical model systems, clinical cohorts, and research techniques and strategies. Identify which aspects of the feasibility study will be conducted at which sites. In the absence of preliminary data, provide compelling rationale for the project and the innovative contribution to PD research. Describe the scientific rigor of the experimental design and the strategies used to minimize bias; include consideration of alternative interpretations. Justify the need for a consortium-based approach to achieve the Aims of the project. Applicants should explain how each research project will interact and synergize with other feasibility projects within the Exploratory Grant.

Additional considerations for Research Feasibility Projects include:

• Applications including clinical cohorts:
• Applicants should provide a timeline for clinical cohort activities, justify the inclusion of a cohort in the Exploratory Grant, and describe requirements for the continuation of that cohort in an NINDS PD CWOW approach.
• 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 biospecimens and clinical data will follow policies and procedures of the NINDS Parkinson's Disease Biomarker Program (PDBP); additional information is available in Section IV. Application and Submission Information, Part 7. Other Submission Requirements and Information, below.
• Every effort should be made to enroll diverse racial and ethnic populations, especially in areas where those populations represent a significant proportion of the local demographic.
• Considering the relatively rapid timeline of the Exploratory Grant, study timeline, including enrollment period, and completion stage, should be described.
• Applications including previously obtained clinical biospecimens:
• Collection and storage protocols should be clearly described and compared to NINDS PDBP protocols. Any differences across protocols should be noted and justified.

Letters of Support:

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

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

NINDS BioSEND repository: include a quote from the BioSEND repository for human biospecimens to be collected during the Exploratory Grant.

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.

Rapid, organized and broad resource sharing are consistent with the goals of the NINDS Udall Centers program. Therefore, the Resource Sharing Plan should address the specific Research Project data and resources to be shared during and that could be shared beyond the proposed Exploratory Grant period.

Applicants are expected to detail how this component will:

• 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.

In a Udall PD CWOW application, applicants will be expected to facilitate sharing of knowledge, data, research resources and biospecimens with the PD research community as appropriate and consistent with achieving the goals of the Udall Centers program

Appendix:

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 Feasibility Project)

When involving NIH-defined human subjects research, clinical research, and/or 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

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

Important reminders:

All PD(s)/PI(s) 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.

NINDS Research Standardization Practices

All human subjects-focused studies in an Exploratory Grant as well as a subsequent NINDS Udall PD CWOW will employ a common set of tools and resources that will promote the collection of standardized biospecimens and data across sites. Therefore, applicants should familiarize themselves with related policies, and relay plans for research standardization of biospecimen collection/distribution/storage, use of Common Data Elements (CDEs) for collection of clinical data, and data collection and storage through the NINDS Data Management Resource (DMR) or other designated NINDS database for exploratory efforts and in future proposed PD CWOW research efforts.

The following information is provided to foster planning efforts.

Biospecimen Collection and Storage

Biospecimens must be collected using protocols of the NINDS Parkinson's Disease Biomarkers Program (PDBP) Laboratory Manual. These procedures are virtually identical to the Parkinson's Progression Markers Initiative of the Michael J. Fox Foundation. If site logistics are challenging regarding the PDBP protocols, then the Alzheimer’s Disease Neuroimaging Initiative (ADNI) protocols could be used as an alternative, pending approval of the NINDS program officer.

PD CWOW applicants will also be expected to utilize NINDS repositories for storage of biospecimens. The NINDS Biospecimen Exchange for Neurological Disorders (NINDS BioSEND) currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva using standardized procedures. The NINDS Human Cell and Data Repository (NCHDR) supports the reprogramming, gene editing, banking and distribution of fibroblasts and induced pluripotent stem cells for neurological disorders, including PD.

Note that costs for 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).

Data Management and Storage

Proposed Exploratory Grant and future Udall PD CWOW research efforts will use the NINDS Data Management Resource (DMR) to store biospecimen-related and clinical data. 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-supported clinical projects, patient consent must allow broad sharing of de-identified data and biospecimen resources though the PD-DMR and NINDS Repositories as appropriate.

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).

Clinical Data Collection and Storage

In order to maximize data standardization across studies, the NINDS strongly encourages researchers to use the NINDS Common Data Elements. The NINDS DMR has developed web-based forms to assure ease of data entry and quality assurance. Some of these assessments may be self-administered to reduce subject and study burden. Subsequent Udall PD CWOW research projects and cores will utilize General and PD-specific CDEs. Additionally, the standard required Clinical Data Elements (CDEs)

(including, but not limited to: demographics, medical history, family history, medications) as described by the NINDS CDE Project and delineated at pdbp.ninds.nih.gov must be used for all clinical components of any given study. Research projects may collect additional clinical information beyond that required by this initiative.

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 the NINDS Biomarkers Repository. 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 FOA.

Subject Consent

Consent forms for Udall PD CWOW clinical studies 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 the designated NINDS Repository and NINDS DMR broad consent requirements.

NINDS Common Data Elements (CDEs).

Induced Pluripotent Stem Cells

Use of Exploratory Grant funds to develop induced pluripotent stem cell (iPSC) lines available or pending through the NINDS Repository is not permitted. If development of iPSC lines is proposed, the specific need for the identified PD challenge must be clearly and strongly justified. Applicants proposing to develop 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) 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 NINDS Repository); 3) for iPSC lines currently available through the NINDS repository, gene correction experiments must be done in these lines; 4) a timeline must be provided for banking of available iPSC lines with the NINDS repository; 5) 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 Parkinson’s Disease Biomarkers Program (PDBP) Data Management Resource (DMR).

Leveraging Existing Research Resources

Applicants are strongly encouraged to leverage 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.

Collaborations with NIH Intramural Researchers

NIH intramural researchers may serve as collaborators or consultants on applications to this FOA.

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 P20 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).

If an Exploratory Grant application is selected for award, funding will be provided by the NIH Intramural Program; budget for intramural activities cannot be included in the P20 application. Budget 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. 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.

According to NIH policy, successfully reviewed applications with substantial intramural involvement will be converted to a cooperative agreement mechanism, with related terms and conditions, prior to award of funds.

At an early planning stage, applicants intending to collaborate with NIH intramural investigators are encouraged to contact the NINDS Scientific/Research Contact(s).

NINDS Morris K. Udall Center without Walls for Parkinson's Disease Research (PD CWOW)

Successful Exploratory Grant awardees will be positioned to submit competitive applications for an NINDS Udall PD CWOW. The PD CWOW FOA is anticipated in fiscal year (FY) 2021 and will utilize the NIH Specialized Center Cooperative Agreement (U54) mechanism. The U54 is a milestone-driven mechanism, the continuation of which is dependent upon the achievement of quantifiable steps within a clearly defined timeframe. Udall PD CWOW milestones will describe the research goal as well as provide objective and quantitative outcomes by which to justify advancing the project, i.e. measures that would be recognizable as appropriate endpoints in the specific scientific area. Synergy must be evident among PD CWOW research projects and cores such that successful completion of proposed milestones could not be accomplished without the CWOW consortium structure. Interventional clinical trials and advanced therapeutic development approaches will be beyond the scope of NINDS Udall PD CWOW efforts; in addition, applications proposing incremental expansion (rather than transformative advancement) of knowledge, data, resources or technologies will not be considered responsive.

The following information is provided to facilitate the development of an Exploratory Grant application.

Required components for a Udall PD CWOW application are expected to include:

• An Overall Section, including but not limited to:
• Statement of and justification for the selected PD challenge.
• Expected impact of the proposed solution.
• Description of synergistic research activities, including:
• -Transdisciplinary pursuit of the defined research challenge.
• -Harmonization of methodologies, technologies, and approaches.
• -Standardization of data and biospecimen collection.
• Justification for the proposed consortium, including unique investigative skills, emergent methodologies, cutting-edge technologies and readily available resources.
• Well-defined milestones.
• A timeline for key CWOW events.
• A minimum of three milestone-driven Research Projects.
• An Administrative Core.
• A minimum of one Scientific Core; each Core must support at least two Research Projects.
• A Clinical Core to support human subjects-focused research (if proposed).
• A Resource Sharing Core.
• Scientific Governance structure, including but not limited to:
• Internal Executive Committee.
• External Steering Committee (to be assembled only subsequent to a successful U54 application).
• Other coordinating committees required for optimal Udall PD CWOW function, e.g.
• Data coordination/access.
• Resource coordination/access.
• Clinical research oversight.
• A dedicated website to provide information to the research community.

Proposed consortia must include the optimal combination of specialized expertise required to resolve the stated challenge using a goal-driven approach. The Program Director/Principal Investigator (PD/PI) must be eminently qualified to provide visionary scientific leadership and effective oversight of consortium administrative activities. The PD/PI must lead the Administrative Core and may lead no more than one other component. Participating investigators should be recognized as world-class experts in their fields, with excellent research productivity and/or the stewardship of multi-site clinical research studies. Teams must be anchored by at least one PD researcher/clinician. To maximize potential for new insights and incorporation of cutting-edge approaches, consortia will actively integrate at least one investigator with primary expertise in another, complementary research area. Inclusion of international collaborators with critical expertise for reaching proposed goals is encouraged. This team structure is intended to enrich the perspectives and methodologies brought to bear on resolution of key issues in PD research. Effort dedicated by the PD/PI and investigators must be commensurate with the goals and timeline of the PD CWOW. The applicant institution must demonstrate ability to lead and coordinate research and administrative activities of the consortium. Participating sites must demonstrate leadership in their area of scientific expertise, as well as propensity to leverage existing resources and technologies to meet stated goals.

All projects should be supported by a timeline and yearly milestones for completion. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment. Note that the NINDS Udall PD CWOW awards will be managed as cooperative agreements; therefore, projects that do not comply with terms, conditions, and established milestones of the award and of this program may be terminated.

By design, Udall PD CWOW are expected to include larger-scale research collaborations, in terms of numbers of investigators and research projects, geographic and institutional diversity of multiple (= 3) research site locations, and dedicated resources, than current Udall Centers (P50). Udall PD CWOW consortia will also be focused on resolution of the identified PD research challenge within a 5-year project period. Due to the goal-driven focus of the planned U54 FOA and inherent differences from aims-driven investigative approach of the P50 Udall Centers, the Udall PD CWOW will not include career development/research training or formal community outreach activities. However, Udall PD CWOW consortia will be encouraged to include a person with Parkinson's or a caregiver on the Steering Committee to provide important perspective. Based on common goals for advancement of PD research, Udall PD CWOW Program Directors/Principal Investigators will become part of the overall NINDS Udall Centers program and will be required to participate in annual meetings to exchange information and ideas. An NINDS PD CWOW will be expected to leverage existing infrastructure and share developed resources, including knowledge, data and reagents, broadly with the research community, consistent with achieving the goals of the Udall Centers program.

A P20 Exploratory Grant Award is not a prerequisite for submission of a Udall PD CWOW U54 application.

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.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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

This FOA supports only those organizational and preliminary research activities directed toward the ensuing submission of an application for an NINDS Udall Parkinson's Disease Center without Walls (Udall PD CWOW). The P20 application must provide substantial evidence to support the potential for a novel, highly skilled investigative team to surmount a critical obstacle in PD. Preliminary data are not required for P20 applications; while investigator-generated data may be included, justification for the proposed work may be provided through literature citations and data from other sources.

Accordingly, reviewers will emphasize the significance of the problem proposed as well as feasibility for success, including the conceptual and organizational framework, the novelty and unique skill set of the investigative team, the strength and timeliness of the proposed planning activities, and the potential transformative impact of a prospective Udall PD CWOW upon the PD field.

Specific to applications involving clinical trials:

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

Accordingly, reviewers will emphasize the fit of proposed clinical studies as well as specific review criteria below.

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.

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

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

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

Reviewers will also be asked to consider the following:

Does the Exploratory Grant proposal identify a critical barrier to progress in the understanding and treatment of PD, and clearly state the related PD research challenge? Does the stated challenge require resolution by a novel, transdisciplinary research consortium using a goal-based approach? If studies on PD-related synucleinopathies are included, are they necessary to address the selected PD research challenge? How significant would the reduction in PD disease burden be if subsequent full-scale efforts are successful? Upon completion of the Exploratory Grant phase, will the research consortium be optimally poised to submit a competitive PD CWOW application?

Is the vision statement sufficiently compelling to support planning for a future Udall PD CWOW effort? Does it detail how the Exploratory Grant will (i) enable pursuit of a fundamental PD research priority; (ii) build an exemplary collaborative team; (iii) gather supportive preliminary data and (iv) demonstrate exceptional potential to pursue a targeted, thematically integrated strategy to remove a critical impediment blocking advancement of the understanding and treatment of PD? Is the proposed focus potentially transformative, rather than an incremental refinement of theoretical concepts, approaches and/or methodologies? Will proposed exploratory efforts establish a "proof of concept" conceptual and organizational framework that will serve as a robust foundation for a full-scale Udall PD CWOW application?

In addition, for applications involving clinical trials:

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

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

Is the PD/PI a world class scientific leader with outstanding productivity and expertise in PD and/or other complementary research area? Does the PD/PI have proven success in the effective leadership of transdisciplinary team efforts? Does the PD/PI have the creativity, drive, seniority and administrative experience to coordinate planning as well as to lead a future NINDS Udall PD CWOW application? Does the PD/PI have current funding (NIH R01 or equivalent) and/or expertise in leading a multi-site clinical research study? Is the effort commitment of the PD/PI reflective of effort required to meet the intensive timeline leading to submission of a PD CWOW?

Does the proposed consortium represent a new, rather than established, collaborative effort?

Is the investigative team comprised of creative, eminently qualified investigators who would be optimal participants in a full-scale Udall PD CWOW to address the stated challenge?

Will team members provide transdisciplinary scientific perspectives required to meet project goals? Is compelling justification provided for selected participants, including their leadership in the proposed area of investigation, expected contributions to the significance and synergy of proposed activities, as well as their unique skillsets and combined knowledge? Is the research team anchored by at least one investigator from within and informed by at least one investigator with expertise from beyond the PD research field? Are the roles of team members clearly defined? Is the effort commitment of consortium investigators appropriate to meet planning timelines and accomplish the goals of the Exploratory Grant?

If investigators currently holding large multi-component grants. including Centers, will participate: are their efforts novel, in terms of team and science, and non-overlapping with their currently supported efforts? Is their commitment sufficient to accomplish the goals of the Exploratory Grant?

Are the qualifications and expertise of the internal Executive Committee well-matched to the stated goals of the Exploratory Grant?

Does the project Administrator have the necessary skills and knowledge to capably partner with the PD/PI and communicate effectively with consortium members?

At the end of the exploratory period, will the proposed research consortium be optimally poised to address the proposed PD research challenge in a Udall PD CWOW application?

In addition, for applications involving clinical trials:

With regard to 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

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

Does the application justify the initiation of a novel, transformative, consortium-based effort to address the identified PD research challenge in a goal-driven manner? Is the proposed consortium novel? Is evidence provided that the proposed planning activities will address the stated challenge through dynamic use of collaborative approaches and resource sharing among participating sites? Are novel means to facilitate communication proposed?

Does the proposed project address a defined and timely research challenge in Parkinson's disease? Is the collaborative project novel? Is it unique in comparison with existing Udall Centers or other large-scale efforts in PD research?

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?

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

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

Does the proposed strategy provide evidence that planning is to be implemented in a strategic, effective and efficient manner? Are the planning activities synergistic and aligned with stated goals of the consortium??

Is an appropriate leadership structure provided, and are administrative, technical and scientific responsibilities clearly laid out? Are available resources at each site detailed? Are details provided regarding how existing tools will be leveraged for research management and broad sharing of data and resources? Are proposed communication and collaboration strategies sufficiently detailed and appropriate? Is sufficient attention paid to fostering collaborations over geographic distance? Is a strategy in place for team continuity during planning and future PD CWOW activities? Are relevant collaborative relationships with non-governmental entities described?

How effective are the plans for the initial planning meeting, teleconferences and/or web meetings, as well as their timeliness and value to effective fostering of consortium-wide communication during the planning process?

Based on information provided, what is the likelihood that the administrative structure, including lines of communication, decision-making processes, coordination across geographic sites, and procedures for resolving conflicts, will support an effective planning effort? Is the internal Executive Committee structured to facilitate and evaluate Exploratory Grant efforts? What is the value to overall efforts of plans for communication with institutional officials at the applicant institution?

Does the overall goal of research feasibility studies address a critical PD research challenge? Are the studies synergistic and aligned with planning activities of the consortium? Are proposed projects based on sound rationale? Are the proposed experimental models justified? Are the experiments rigorously designed?

Does the timeline provide sufficient detail regarding yearly objectives and goals and end with an approximate Udall PD CWOW application submission date?

If applicable, does the application include a description of standardized data and biospecimen collection methods to be utilized by the consortium in a future PD CWOW? Are related NINDS policies and procedures acknowledged?

In addition, for applications involving clinical trials:

Does the application address the following, if applicable?

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

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?

Does each of the sites contribute unique and complementary expertise and resources that will be used optimally to meet the defined challenge? Will the proposed research environments contribute to the success of the Exploratory Grant, and the subsequent formation of a future Udall PD CWOW?

Does the applicant institution demonstrate excellent potential for effective coordination of the Exploratory Grant and the subsequent Udall PD CWOW effort?

Is there evidence of institutional commitment, from both applicant and participant institutions, to the goals of the research consortium? How appropriate are institutional commitments proposed to support the goals of the research consortium during the planning process, and also during a potential future CWOW project period?

How well will existing resources at each site be leveraged to meet the goals of a Udall PD CWOW? If other large-scale PD projects exist at participating institutions, how well will potential resources and collaborations be utilized?

In addition, for applications involving clinical trials:

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

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

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

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

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

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

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

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

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

Not Applicable.

Not Applicable.

Not Applicable.

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

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

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic 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 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 appropriate 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.
• Areas of complementarity to existing NINDS Udall Centers and other ongoing, large-scale PD research efforts.
• One exploratory grant may be awarded at any one institution).
• Overlapping efforts of an investigator across multiple Exploratory Grant consortium applications will not be supported.
• Potential to directly and effectively address the stated essential challenge in PD research.

Additional NINDS considerations during the selection of Exploratory Grant applications include:

• The qualifications and experience of the PD/PI and other key personnel.
• The novelty of the proposed research consortium.
• The statutory and program purposes to be accomplished.
• The potential to rapidly advance PD research using a goal-driven approach to resolve an essential challenge.

The NINDS will consider the full scope of PD programmatic activities when making funding decisions; applications proposing goals identical to or largely overlapping with active P50 Udall Centers and/or other large-scale PD research efforts will receive lower program priority. The NINDS will prioritize innovative applications with greatest potential to develop a subsequent Udall PD CWOW application.

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 of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

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

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

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

NINDS Fiscal Policy: Awards are subject to NINDS Fiscal Policy for the relevant fiscal year.

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

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

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 on-time submission, 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 processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

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

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

Tijuanna Decoster, PhD, MPA
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@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.