Studies in Parkinson's Disease Biomarkers Discovery (U01)

Studies in Parkinson's Disease Biomarkers Discovery (U01) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS). The purpose of this funding opportunity is to support hypothesis-driven clinical research to discover biomarkers that will improve the efficiency and outcome of Phase II clinical trials for Parkinson's Disease and to support the collection of clinical data and new biological spe…

Expired PAR-18-800: Biomarkers Discovery In Parkinsonism (U01 Clinical Trial Optional) This notice has expired. Check the NIH Guide for active opportunities and notices. Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Stroke ( NINDS ) Funding Opportunity Title Biomarkers Discovery In Parkinsonism (U01 Clinical Trial Optional) U01 Research Project – Cooperative Agreements Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The purpose of this funding opportunity announcement (FOA) is to support hypothesis-driven research to discover human biomarkers in Parkinson’s disease and other Parkinsonian syndromes, as a component of the NINDS Parkinson’s Disease Biomarkers Program (PDBP).

This FOA encourages biomarkers discovery projects in: 1) genetically causal Parkinson's disease, especially for particular sub-types of Parkinson's Disease (PD), including genetic cohorts, biologically defined cohorts of idiopathic PD, or ethnic subgroups of idiopathic PD; 2) the differentiation of synucleinopathies (such as PD and Multiple System Atrophy (MSA) from tauopathies (such as Progressive Supranuclear Palsy and Corticobasal degeneration); or 3) to improve diagnostic differentiation between idiopathic/subtypes of PD and these disorders, as well as from Essential tremor.

To further advance research in this area, broad sharing of biospecimens and associated data is a critical feature of the PDBP generally and of this FOA specifically. A timeline including milestones, which will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years, is required for all studies.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date September 6, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date .

AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from 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.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Go to Grants. gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.

gov; and track your application in eRA Commons. Learn more about the various submission options . Part 1.

Overview Information Part 2. Full Text of the Announcement I. Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Funding Opportunity Description This FOA is part of a broader Parkinson’s disease biomarkers program (PDBP) at National Institute of Neurological Disorders and Stroke (NINDS).

This program underscores the intent of NINDS to facilitate the discovery and development of biomarkers to improve the efficiency and outcome of Phase II or III clinical trials and advance therapeutic development for Parkinson’s Disease (PD) and related disorders. Clinically, Parkinson's disease is heterogeneous, and subtypes are recognized based on age of onset, predominant clinical features and progression rate.

The wide spectrum of clinical manifestations in parkinsonism and its evolving chronic course contribute to numerous pitfalls in clinical trial design. The term PARKINSONISM has been used to describe neurologic disorders characterized by the presence of at least three of the following: tremor, rigidity, gait disturbance, and bradykinesia. The most common cause of parkinsonism is PD.

Differential diagnosis of PD from other parkinsonian disorders, such as Essential Tremor (ET), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), can be clinically challenging, particularly during the early disease stages. There is no definitive biomarker for PD or for other atypical neurodegenerative parkinsonian disorders during life.

This FOA seeks to better fill these scientific gaps. Further definition of clinical phenotypes of and their correlation with pre-diagnostic manifestations could be crucial, especially if associated with genetic and biochemical markers. Another goal of this FOA is to allow studies to discover biomarkers of biological and genetic subtypes of types of Parkinsonism, which in turn may allow more targeted therapies to be developed.

The accumulation of a-synuclein aggregates is the hallmark of Parkinson’s disease, and more generally of synucleinopathies (including, for example, MSA). The accumulation of tau aggregates is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, Parkinsonism can be the result of a tauopathy, including, for example in CBD and PSP.

Studies evaluating biomarkers to differentiate synucleinopathies from tauopathies have clear translational relevance, considering that the therapeutics for these two biologically different causes of Parkinsonism are likely to have different therapeutic strategies. Some published studies have demonstrated that there are multiple forms of PD, and that these may be different in various ethnic groups.

However, ethnic minority populations are often under-represented in clinical studies, including, currently, PDBP. Subgroups of PD may involve multiple different etiological or pathological processes, and therefore, therapeutic approaches in these sub-groups may also require different strategies.

Examples of biomarker discovery studies that would be appropriate under this FOA include: Examples of biomarker discovery studies that would be appropriate under this FOA include: Studies of biomarkers for PD or other PDism disorders in genetically defined cohorts. Studies of biomarkers for PD or other PDism disorders in ethnic cohorts. Studies that identify biomarkers for differentiating synucleinopathies from tauopathies.

Studies of either clinical or laboratory based biomarkers to identify subtypes of idiopathic Parkinson's disease. Studies of non-PD Parkinsonism (MSA, CBD, PSP) that identify biomarkers to differentiate these disorders from controls, those that differentiate these from PD, and/or from each other. The use of cutting edge technologies or approaches such as telemedicine or mobile devices is welcomed.

Required Use of the PDBP Data Management Resource The PD Data Management Resource (PD-DMR) must be used for data management by awardees under this FOA. The PD-DMR provides data coordination for the Parkinsonism research community through its web-based data management system. It also provides tools for both the collection and quality assurance of data in a standardized format.

The PD-DMR synchronizes efforts across government, industry, and other non-government organizations involved in PD and related disorders research through the creation of a federated database. It is expected that the following clinical tools and scales will be used in addition to those already required (see http://pdbp. ninds.

nih. gov/researcher ), for the relevant subject populations, and that data will be entered into the PD-DMR by the research team in real time for each clinical assessment.

The MDS Unified Parkinson's Disease Rating Scale (MDS-UPDRS) The Progressive Supranuclear Palsy (PSP) Rating Scale TETRA (Tremor Action Group Tremor Rating Assessment) Scale The Unified Multiple System Atrophy Rating scale The Neuropsychiatric Inventory (NPI) 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.

Banking of Specimens via the NINDS Biomarkers Repository Biospecimens must be collected per NINDS Biomarkers Repository protocols and procedures, and all specimens collected must come from individuals who have consented to banking and sharing broadly with academia and industry. Sample collections must also adhere to PDBP standards. Note that costs for collection are NOT included as a component of the NINDS Biomarkers 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 the NINDS Biomarkers Repository website for more information about samples banked at the repository ( https://www. biosend.

org ). In addition, applicants are advised to consult with NINDS Biomarkers Repository staff to obtain a quote for biospecimen banking costs (email: [email protected] ). For applications proposing to include neuroimaging, all formats should be compatible with the Medical Image Processing, Analysis, and Visualization tool (MIPAV: http://mipav.

cit. nih. gov/ ).

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. The development of new databases and/or biospecimen repositories will not be supported under this FOA. This FOA is only for studies related to human biomarkers.

This FOA will not support studies that develop general methods; all applications must be specific to PD and Parkinsonian disorders research. Clinical trial applications are more appropriate for mechanisms listed via https://www. ninds.

nih. gov/Current-Research/Research-Funded-NINDS/Clinical-Research . Studies of assay optimization, validation, or replication of idiopathic Parkinson's Disease using the PDBP extant sample collection in combination with other collections may be more appropriate for NOT-NS-18-015 A timeline including milestones is required for all studies.

Annual milestones will provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Achievement of milestones will be evaluated by NINDS, and funding of non-competing award years will depend on milestone accomplishment.

Both data and biospecimen collection must meet DMR and NINDS repository standards. Due to the unique requirements of the NINDS PDBP and the NINDS Biomarkers Repository, applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application (see Agency contacts, Section VIII).

This early contact will provide an opportunity to clarify the applicant's understanding of NINDS’ policies and guidelines, including the scope of projects within the PDBP. These discussions also provide important information and guidance on how to develop an appropriate timeline and milestone plan. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this FOA.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Optional: Accepting applications that either propose or do not propose clinical trial(s) Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is five years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) 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 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 Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement , are not allowed. Applicant organizations 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement. 3. Additional Information on Eligibility 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 ) Section IV. Application and Submission Information 1.

Requesting an Application Package Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications .

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in Part 1.

Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Research Strategy: A milestone plan, under separate headings, must be included in the Research Strategy section of the application.

Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Milestones should include timely subject recruitment (if relevant), complete, clean and accurate data submission timelines including specifics of types of data to be submitted, and quality accepted collection and submission of biospecimen samples milestones.

For new cohort studies, the milestone plan must include a timeline for recruitment, number of visits per year and over the course of the study, and biospecimen collection and must mirror the timeline schedule of the PDBP.

In the case of ancillary studies that will require additional clinical assessments and/or require additional biospecimen collection, the milestone plan should also outline the number of subjects from the parent cohort required for the ancillary study, the clinical sites involved and the timeline for data/biospecimen collection.

This can reference but should not duplicate information submitted on the PHS Human Subjexts-Clinical Trial Information Form. Note : Inclusion of a tissue donation plan is strongly encouraged for applications recruiting clinical populations where the clinical diagnosis is uncertain in the early stages of disease or may change over the time course of disease.

If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental or non-governmental entities, letters of support detailing the terms of collaboration and data sharing must be included. If utilization of extant samples is proposed as a component of the study, letters of support or approval for use of those samples must be included.

If samples include those adjudicated by the PD-BRAC, a letter indicating BRAC approval must be included. Approval for samples occurs through submission of an online application followed by PD-BRAC review . For studies ancillary to parent studies, review and approval for the use of samples from the parent study must be completed and a letter of approval must be submitted.

Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Clinical Data should be submitted via ProFoRMs in real time to the DMR via provided web-based forms; if real time submission is not possible, then all data must be submitted within one day of collection to the DMR . For ancillary studies using existing cohorts and infrastructure, broad sharing of de-identified clinical, laboratory data and biospecimens must not be restricted by parent study policy or procedures.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

The Appendix must contain the following materials (if appropriate to the study): If an ancillary study to an existing project, include also: The protocol for the parent study Investigator's brochure, if applicable, for the parent clinical study Consent forms (for both the parent clinical study and the ancillary studies, if different) Written agreement to conduct the ancillary study from parent clinical study sponsors.

IRB approval of the informed consent form(s) is not required at the time of submission of the application. However, drafts of informed consent form(s) must be included.

PHS Human Subjects and Clinical Trials Information When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions: All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide must be followed. 3.

Unique Entity Identifier and System for Award Management (SAM) 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 4. Submission Dates and Times Part I. Overview Information contains information about Key Dates and times.

Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants.

gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants.

gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time.

If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission. Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 5. Intergovernmental Review (E.

O. 12372) 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 . 7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.

Paper applications will not be accepted. Applicants must complete all required registrations before the application due date. Section III.

Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues .

For assistance with application submission, contact the Application Submission Contacts in Section VII . Important reminders: All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package.

Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

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

Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials 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. Section V.

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

For this particular announcement, note the following: This FOA intends to support studies in biomarker discovery that will have or do one or more of the following: a significant impact on the diagnostic accuracy or impact on assessment of the disease progression in PD and/or Parkinsonism improve the ability to differentiate PD from other types of parkinsonism during life differentiate synucleinopathies from tauopathies during life lead to the discovery, development, or replication of biomarkers which facilitate a better understanding of stratification of disease that will be useful for future therapeutic trials.

Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding of such biomarkers.

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

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

Does the project address an important problem or a critical barrier to progress in the field? 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? Does the project complement existing studies or address a gap in the field of Parkinson's disease and Parkinsonism biomarkers? Is the cohort or subtype of parkinsonism or Parkinson's disease proposed for study appropriate to inform future therapy development?

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