Analytical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01) is a grant from the National Institute of Neurological Disorders and Stroke (NINDS) that funds analytical validation studies for candidate biomarkers relevant to neurological and neuromuscular diseases.

Funded projects establish that a proposed biomarker assay is accurate, reproducible, and fit for purpose before advancing to clinical validation stages. This funding opportunity has been updated to align with current NIH priorities, and applicants should review the full announcement carefully before submitting.

Eligible applicants include nonprofits, universities, state and local governments, for-profit organizations, small businesses, and individuals. The application deadline is June 22, 2026.

PAR-25-055: Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Funding Opportunity Title Clinical Validation of a Candidate Biomarker for Neurological or Neuromuscular Disorders (U01 Clinical Trial Optional) U01 Research Project – Cooperative Agreements Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. January 14, 2025 - Notice of Change: Only BESH CT Applications Accepted in PAR-25-050, PAR-24-098, PAR-25-055, PAR-24-096. See Notice NOT-NS-25-009 .

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II Small Business Innovation Research (SBIR) Cooperative Agreements - Phase II Research Project (Cooperative Agreements) See Section III. 3. Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to enable clinical validation of strong candidate biomarkers for neurological and neuromuscular disorders and conditions.

Specifically, the goal of this PAR is to enable the rigorous clinical validation of biomarker measurements within the clinical population of interest to establish the clinical sensitivity and specificity of the biomarker consistent with FDA guidelines.

This PAR assumes that 1) a candidate biomarker has already been identified, 2) detection method technology has already been developed and analytically validated, and 3) the research and/or clinical need and potential context of use has been identified.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. 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.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of 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 Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description A biomarker is a defined characteristic that is measured as an indicator of a normal biological process, pathogenic process, or responses to an exposure or intervention, including therapeutic interventions.

Biomarker modalities are diverse, and can include ‘omics, imaging, behavioral, digital and physiologic endpoints. Because the measurement of the biomarker is integral to defining the biomarker, it is necessary to describe the biomarker in terms of its biological source or matrix, measurable features, and the analytic method used to measure it (“detection method”).

Biomarkers are critical to the discovery and development of therapeutics and can serve a variety of functions such as verifying therapeutic target engagement, improving trial design by patient stratification, and facilitating clinical care decisions.

Despite the active pace of discovery of novel biomarker candidates, few biomarkers progress beyond discovery to the robust analytical and clinical validation needed for use in Phase II and Phase III clinical trials.

Thus, there is a critical need to advance validation of biomarkers to improve public health, particularly for disorders of the nervous system where advancing therapeutics from discovery to the market are notoriously challenging. Validation of biomarkers for all neurological and neuromuscular disorders within NINDS’ mission are within scope and may include a context of use focused on any part of the age spectrum.

This NOFO is intended to address the gap in biomarker validation by encouraging rigorous clinical validation of the biomarker detection method for one or two specified context(s) of use. Definitions of terms used in this NOFO: Context of Use (COU): A statement that fully and clearly describes the way the biomarker is expected to be used.

The COU should include the biomarker category (susceptibility/risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic/response, or safety), the modality, method of detection, and clinical population characteristics. Context of use statements are discussed extensively in the Framework for Defining Evidentiary Criteria for Biomarker Qualification developed by the Biomarkers Consortium: https://fnih.

org/sites/default/files/final/pdf/Evidentiary%20Criteria%20Framework%20Final%20Version%20Oct%2020%202016. pdf Concept: In a regulatory context, the concept is the aspect of an individual’s clinical, biological, physical, or functional state, or experience that the assessment is intended to indicate or reflect. Detection method: The method(s) used for measuring the biomarker(s).

Analytical Validation: A process to establish that the performance characteristics of a test, tool, or instrument are acceptable in terms of its sensitivity, specificity, accuracy, precision, and other relevant performance characteristics using a specified technical protocol (which may include specimen collection, handling and storage procedures).

This is validation of the test’s, tool’s, or instrument’s technical performance to measure the biomarker(s) of interest. Clinical Validation: A process to establish that the test, tool, or instrument acceptably identifies, measures or predicts the concept of interest.

Clinical validation establishes the data needed to reach conclusions or interpret the results of the biomarker(s) readout, and the level of confidence for these interpretations. Composite biomarkers/biomarker signatures: when more than one biomarker is being validated for the same context of use (e.g., a panel of biomarkers, or set of features used as a composite indicator).

Clinical Outcome Assessment (COA): a measure that describes or reflects how a patient feels, functions, or survives (includes patient-reported outcomes, observer-reported outcomes, clinician-reported outcomes, and performance outcomes).

Digital Biomarker: The term “digital biomarker” is widely used to mean assessments that include both biological processes (such as changes in heart rate or galvanic skin response) as well as performance assessments (such as measurements derived from accelerometers).

Both digital biomarkers and digital performance assessment are within scope of this NOFO, however other patient-reported outcomes, observer-reported outcomes, and clinician reported outcomes are not within scope. Biomarker categories as defined in the Biomarkers, EndpointS, and Other Tools (BEST) Resources (https://www. ncbi.

nlm. nih. gov/books/NBK338448/) include: Monitoring biomarkers to track the success of a therapeutic intervention or the disease progression Diagnostic biomarkers used to detect or confirm presence of a disease or condition of interest or to identify individuals with a subtype of the disease.

Prognostic biomarkers for predicting outcomes Predictive biomarkers for differentiating individuals based on favorable or unfavorable effect from a therapeutic or other intervention Pharmacodynamic/response biomarker that indicates biologic activity of a medical product or environmental agent without necessarily drawing conclusions about efficacy or disease outcome or necessarily linking this activity to an established mechanism of action.

Safety biomarkers to indicate the likelihood, presence, or extent of an adverse effect Susceptibility/risk biomarkers that indicate the potential for developing a disease or medical condition in an individual who does not currently have a clinically apparent disease. This NOFO supports research to conduct clinical validation of a biomarker or biomarker signature or composite biomarker for one or two specified context(s) of use.

For the purpose of this NOFO, the term “Biomarker(s)” will be used interchangeably with biomarker signature and composite biomarkers.

Premise for the utility of the biomarker(s) should include evidence that the biomarker(s) has undergone preliminary testing in an appropriate clinical population, using either prospective or retrospective data or samples, and shows sufficient clinical sensitivity and specificity to predict or measure the relevant clinical or biological concept of interest to warrant additional investment.

In addition, applications to this NOFO should include evidence that the detection method for the biomarker has already been developed and analytical validated with sufficiently reliable performance for in the proposed context of use.

Earlier stage research that still needs to conduct clinical proof of concept studies to establish the relationship between candidate biomarkers with a concept of interest (with or without detection method development) should consider applying to the companion NOFO, PAR-22-089 “Development of Biomarkers or Biomarker Signatures for Neurological and Neuromuscular Disorders”.

Alternatively, studies that are seeking to conduct final analytical validation research should consider the companion NOFO “Clinical Validation of Biomarkers for Neurological and Neuromuscular conditions”.

This funding opportunity uses a cooperative agreement, milestone driven mechanism that enables significant input from NIH staff to assist investigators with preparing and evaluating their analytical validation strategy through milestone negotiation.

The Analytical Validation NOFOs and companion Clinical Validation NOFOs are designed to help gather the data package needed for clinical trial readiness and may be used to support a submission to the FDA’s Biomarker Qualification Submission or to the FDA’s Center for Devices and Radiological Health, if applicable. For more information on the Biomarker Qualification program see: https://www. fda.

gov/Drugs/DevelopmentApprovalProcess/DrugDevelopmentToolsQualificationProgram/BiomarkerQualificationProgram/default. htm Application Characteristics One or two clearly defined context(s) of use A strong justification for the clinical and/or research need of the biomarker(s) and the detection method for the context(s) of use.

Justification of feasibility, including potential added clinical burden and cost, of incorporating the biomarker into clinical trials or clinical practice (as appropriate for the context(s) of use). A clear and well justified study design and statistical design(s) A direct comparison to existing biomarkers or clinical outcome assessments used for the same COU, if applicable.

A multi-site design to demonstrate reliable results across sites in a sufficiently representative cohort, or a strong scientific justification why only one site is needed. Evidence of scientific rigor in the supporting literature underlying the premise, the preliminary data, as well as in the research strategy, design, execution, and interpretation of the proposed studies.

A clear and feasible timeline with quantitative annual milestones that demonstrate continued feasibility and progress towards the project’s success (see section IV “Other Project Information”) A team management plan (see section IV “Other Project Information”) If applicable, an Intellectual Property (IP) plan (see section IV “Other Project Information”) Clinical Validation should include the following metrics with use of FDA guidance standards appropriate for the Context of Use: Sensitivity and specificity of the biomarker within the Context of Use, including methods for binary and/or continuous analysis.

Area Under the Curve (AUC) as determined by Receiver Operator Characteristic (ROC) Analysis Estimation of the prevalence of the marker within subjects or patients for the intended clinical context. Establishing the appropriate thresholds or reference ranges for the biomarker for decision-making within the context of use.

Positive Predictive Value (the probability that a positive screening test result is true, taking into account the prevalence of the disease or condition in the population being measured). Negative Predictive Value (the probability that a negative screening test result is true, taking into account the prevalence of the disease or condition in the population being measured).

Collaborations and Consultants Multidisciplinary collaboration among scientific investigators, clinical scientists, disease/biology matter experts, statisticians, regulatory expertise, and other academic/industry experts relevant to the context of use in the application as well as clinical and laboratory staff are an integral part of the application.

Investigators are also encouraged to form collaborations/obtain consultants with individuals knowledgeable in relevant regulatory processes and/or statisticians knowledgeable in clinical trial design. Leveraging Existing Resources Where applicable, applicants are encouraged to leverage existing research resources for their studies.

Such resources may include clinical biospecimen samples from the NINDS Human Biospecimen and Data Repository (BioSEND; https://biosend. org/ ) or other existing biospecimen, imaging and data repositories. Leveraging the resources of ongoing clinical trials or clinical studies supported through other Federal or private funds is also encouraged.

Rigor, Reproducibility, Data Sharing and Intellectual Property NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency ( https://grants. nih.

gov/policy/reproducibility/guidance. htm ) and provides additional guidance to the scientific community ( https://www. ninds.

nih. gov/Funding/grant_policy ). For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner.

If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

To improve reproducibility and community uptake, investigators are generally expected to share code/scripts, analytic tools/statistical models, protocols/processes and metadata before the end of the project’s period of performance.

If there is a plan to commercialize aspects of the project such as analytic software, applicants should consult with their tech transfer office when developing the Data Management and Sharing Plan and intellectual property plan. Budgets should reflect any costs associated with these efforts. Information on many available NIH supported or frequently used repositories is available at: https://www.

nlm. nih. gov/NIHbmic/nih_data_sharing_repositories.

html Applicants collecting biofluid samples from prospectively enrolled study participants are encouraged to share samples through the NINDS biomarker repository, BioSEND ( https://biosend. org/ ) to provide the broader scientific community with a data resource for hypothesis generation and test validation. Applicants should contact BioSEND to incorporate sharing plans and cost in their application.

Pre-Application Consultation Applicants are strongly encouraged to consult with NINDS Program Staff early on during the planning for an application. This early contact will provide an opportunity to discuss and clarify NINDS policies and guidelines, including the scope of the project relative to the NINDS mission and intent of this NOFO.

These discussions can also provide any needed clarification regarding development of an appropriate timeline and milestone plan and guidance for requesting approval of budgets that exceed $500,000 direct cost in any given year. Applications within the top scoring meritorious range will be considered for funding.

Within that range, priority may be placed on applications that fill a critical program gap to ensure biomarker development that is reflective of the breadth of disorders and conditions within NINDS’s mission.

Additionally, priority will be given to biomarkers that: 1) address an unmet medical need, 2) are supported by a strong biological rationale, 3) include a carefully designed plan for performance evaluation, 4) include a plan for standardization of samples and data collection for use in validation and 5) provide a strong justification for the utility of the biomarker in the clinical setting or for use in clinical trial design.

Applications Not Responsive to this NOFO Non-responsive studies include: clinical trials or clinical research where the primary intent is to develop therapeutic agents or devices, clinical trials or clinical research to evaluate a therapeutic agent or device’s clinical safety, efficacy, effectiveness, and/or clinical management, pre-clinical research using animal models, applications where the primary intent is to validate clinical outcome assessments rather than biomarkers, applications that do not include a context of use statement applications that do not include milestones, applications that are not within the NINDS mission Non-responsive applications will be administratively withdrawn without review.

See Section VIII. Other Information for award authorities and regulations. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information Cooperative Agreement: A financial assistance 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 NOFO. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. 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 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 Organizations) 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 must complete and maintain the following registrations as described in the How to Apply-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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registration; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active 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 their organization to develop an application for 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 How to Apply- Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

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, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

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 NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

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

Timeline and Proposed Milestones (required; 3 pages maximum): Milestones should describe project decision points with quantitative metrics for go/no-go decision making throughout the funding period. Annual quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties.

Milestones will be used to monitor project progress as part of the evaluation for continued funding by the Program Official and Project Scientists. For each milestone, provide a brief description of the success criteria and justification for those criteria.

Quantitative milestones are dependent on the project but should include items such as: Progress metrics such as enrollment goals, sample and data collection goals, key experiments conducted, etc. Performance metrics such as reaching target sensitivity, specificity, precision and accuracy thresholds, achieving target inter and intra rater reliability and achieving other QA/QC thresholds needed for successful analytical validation across sites (if applicable) and operators.

If applicable, planned interactions to obtain feedback or submit qualification packages to regulatory agencies such as the FDA or CMS such as, but not limited to, filing for qualification as a medical device development tool, letter of intent for biomarker qualification, CLIA certification, or plans to request a FDA Q-Submission meeting A Gnant chart for the timeline of attaching each milestone is encouraged.

Team management plan (required; 3 pages maximum): All applicants must include a team management plan that describes the workflow of the team/key personnel.

Applicants are strongly encouraged to form multidisciplinary teams that consist of clinical scientists, disease/biology matter expertise, statisticians, particularly those with clinical trial design expertise, regulatory expertise, and other academic/industry experts relevant to the modalities used in the application.

Describe how the team will work together (e.g., data generation, reporting of data and integrated review across teams with various disciplines, decision-making, etc.) over the course of the project and include letters of support (below). This section should be complementary to the “Multiple PD/PI Leadership Plan” leadership plan by focusing on how the project will be managed across sites, PIs, co-Is and consultants.

Effective project management is a critical component of achieving the program goals, especially as the team size increases.

Elements to consider include: Organizational structure, team composition, and roles Shared vision, contributions, and distributed responsibility for decision-making Resource sharing and allocation Coordination and communication Intra-team data sharing, archiving, and preservation Associated clinical trial protocols and consent forms (required if applicable; no page limit): Applications that propose to conduct ancillary studies to clinical trials and/or leverage samples/data collected from previous clinical trials must include the clinical trial protocols and consent forms used in the trials.

Intellectual Property Plan (if applicable; 1 page maximum): Applicants are encouraged to prepare this section in consultation with their institutions' technology transfer officials.

Applicants should describe any constraints of which they are aware that could impede commercialization (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar biomarkers that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program.

If the IP of the detection method device/technology/software is owned by an entity other than the applicant's institution, then a letter of support should be obtained indicating there will not be any limitations imposed on the studies or the product which would impede achieving the goals of the funding program.

If patents have been filed around the biomarker detection method(s) used in this application, then the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated USPTO links, if applicable. Letters of Support (if applicable; no page limits): Applicants should include letters of support from consultants, contractors, and collaborators.

Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, consultants, and / or BioSEND if biospecimens are being collected. If applicable, include a letter of support from the technology transfer official who will be managing intellectual property associated with this project.

If research will be performed at more than one institution, include a letter of support from each institution clarifying how intellectual property will be shared or otherwise managed across the institutions.

If collaborating with a private entity, include a letter of support that addresses any agreement to provide agent(s), any limits on the studies that can be performed with said agent(s), any limitations on sharing of data (including negative results), and whether a licensing agreement(s) will be needed and in place once the project is funded.

This letter should come from a high official within the private entity who has authority to speak on these issues. 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 existing biospecimens are to be used, include letters of support or approval for use of those samples, including those banked at BioSEND . For example, if samples include those adjudicated by the Parkinson's Disease Biospecimen Review Access Committee (PD-BRAC), a letter indicating BRAC approval should be included ( https://pdbp. ninds.

nih. gov/pd-brac) SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: This NOFO supports the clinical validation of biomarker(s), that are fit for the purpose for one or two contexts of use.

Context of Use and Specific Aims Context of Use : briefly describe the contexts of use which must include both the BEST biomarker category and the biomarker’s intended use in therapeutic development or clinical practice (no more than two contexts of use should be included).

Specific Aims Briefly describe the project aims, including the questions to be answered and the performance outcomes and characteristics needed in order to be used and interpretable for the stated Context of Use(s). A scientific hypothesis is not required for this type of application.

The Research Strategy Section should include the following sections and address the following topics: Clinical Context and Unmet Need: Provide a paragraph under the heading “Context of Use” that expands on the Context of Use described in the aims page, and explains how the biomarker/biomarker signature/composite is intended to be used to advance therapeutic development or in clinical practice, including the specific clinical population(s) where the biomarker is intended to be used.

Describe