HT942526ALSRPCOBA_GG.pdf

This program announcement must be read in conjunction with the General Application Instructions, version CD26_01.

Program Announcement for the Defense Health Agency

Amyotrophic Lateral Sclerosis Research Program

Clinical Outcomes and Biomarkers Award

Funding Opportunity Number: HT942526ALSRPCOBA

Pre-Application Due: June 24, 2026

Application Due: September 30, 2026 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 2

Content

Before You Begin 3

Basic Information Summarizes the funding opportunity, funding details, submission deadlines and review dates

Eligibility Details eligibility factors for the applicant organization and Principal Investigator

Program Description Describes the program mission and intent of the Clinical Outcomes and Biomarkers Award;

provides key award information and considerations; and outlines funding details

Application Contents Presents the two-step application process and instructions for preparing a pre-application and full application

Submission Requirements Provides locations for application packages, instructions for submitting pre-applications and full applications, and describes application verification

Application Review Information Outlines the processes for application compliance review, pre-application and full application selection/notification, and risk assessment. Also, details the review criteria for pre-application screening and both tiers of the CDMRP application review process – Peer Review and Programmatic Review

Federal Award Notices Outlines what a successful applicant can expect if recommended for funding

Post-Award Requirements References policy requirements for funded research; outlines reporting requirements and restrictions related to Principal Investigator changes and institutional award transfers

Other Information Outlines criteria for administrative actions including application rejection, modification, withdrawal and withhold

Appendix 1 Includes a checklist for all full application components to facilitate application submission

Appendix 2 Acronym List

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Before You Begin

• Active SAM.gov, eBRAP.org and Grants.gov registrations are required for application submission. User registration for each of these websites can take several weeks or longer.

Each applicant must ensure their registrations are active and up to date prior to application preparation.

• Read this funding opportunity announcement in the order it is written before beginning to prepare application materials. It is the responsibility of the applicant to determine whether the proposed research meets the intent of this funding opportunity and that all parties meet eligibility requirements.

• To support application preparation, additional resources are available including an application process FAQ, a Guide for Intragovernmental & Intramural Applicants and a CDMRP Video Series detailing the application process.

Who to Contact for Support

This document uses internal links; you can go back to where you were by pressing the Alt + left arrow keys (Windows) or command + left arrow keys (Macintosh) on your keyboard.

Click to be taken to additional guidance and instructions within the General Application Instructions (GAI).

eBRAP Help Desk

301-682-5507 help@eBRAP.org

Questions regarding funding opportunity submission requirements, as well as technical assistance related to pre-application or intramural application submission.

Grants.gov Support Center

800-518-4726 International: 1-606-545-5035 support@grants.gov

Questions regarding Grants.gov registration and Workspace.

https://sam.gov/ https://ebrap.org/eBRAP/public/index.htm https://grants.gov/register https://cdmrp.health.mil/#:~:text=Frequently%20Asked%20Questions%20%C2%BB https://cdmrp.health.mil/#:~:text=Guide%20for%20Intragovernmental%20%26%20Intramural%20Applicants https://ebrap.org/eBRAP/public/Program.htm#:~:text=Journey%20of%20an,Tier%20Review%20Process mailto:help@eBRAP.org mailto:support@grants.gov https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

Section Shortcuts Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements

Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

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1. Basic Information About the Funding Opportunity

Summary: The fiscal year 2026 (FY26) Amyotrophic Lateral Sclerosis Research Program (ALSRP) Clinical Outcomes and Biomarkers Award (COBA) supports the development and/or validation of clinical outcomes and biomarkers to enrich clinical trials in amyotrophic lateral sclerosis (ALS). Projects can be relevant to a specific therapy, a class of therapeutics, or to a specific ALS subtype (such as a particular genetic mutation) and do not have to broadly apply to all patients.

Distinctive Features: To meet the intent of the funding opportunity, applications may address clinical biomarkers and/or clinical outcomes. This may include the identification, development, and/or validation of promising biomarkers for ALS, which may include, but are not limited to susceptibility/risk, diagnostic, monitoring/disease progression, prognostic, predictive, response, or safety biomarkers. Clinical Outcomes projects may focus on the identification, development, and/or validation of clinician-, observer-, or patient-reported, and/or performance outcome measures for ALS. Projects may include the optimization of current outcome measures already in use.

Applications may utilize digital health measures, including wearable devices, smart-phone sensors, video or voice recordings, imaging studies, or other devices which record disease-relevant physiological data and/or outcomes.

Community Collaboration is an important element of the FY26 ALSRP COBA. Applicants will be expected to articulate how the proposed research question or study design was informed by the ALS lived experience community.

Funding Details: The Congressionally Directed Medical Research Programs (CDMRP) expects to allot roughly $7.0 million (M) to fund approximately seven COBA applications with total cost caps of $1.0M per award. The maximum period of performance is three years. It is anticipated that awards made from this FY26 funding opportunity will be funded with FY26 funds, which will expire for use on September 30, 2032. Awards supported with FY26 funds will be made no later than September 30, 2027.

Submission and Review Dates and Times

• Pre-Application (Preproposal) Submission Deadline: 5:00 p.m. Eastern Time (ET), June 24, 2026

• Invitation to Submit an Application: August 3, 2026

• Application Submission Deadline: 11:59 p.m. ET, September 30, 2026

• End of Application Verification Period: 5:00 p.m. ET, October 6, 2026

• Peer Review: November 2026

• Programmatic Review: January 2027

Announcement Type: Initial

Funding Opportunity Number: HT942526ALSRPCOBA

Assistance Listing Number: 12.420

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2. Eligibility Information

2.1. Eligible Applicants

2.1.1. Organization

Extramural and intramural U.S. Department of War (DOW) organizations are eligible to apply, including foreign and domestic organizations, for-profit and nonprofit organizations, and public or private entities.

2.1.2. Principal Investigator

Independent investigators affiliated with an eligible organization are eligible to be named Principal Investigator (PI) on the application, regardless of ethnicity, nationality or citizenship status. An investigator may be named as PI on no more than three FY26 ALSRP applications across all award mechanisms, in any combination.

2.2. Cost Sharing

Cost sharing is not an eligibility requirement.

2.3. Other

Awards are made to eligible organizations, not to individuals. Refer to the GAI for additional recipient qualification requirements.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Content_Form_Full_App_Submission:~:text=pre%2Dapplication%20submission.-,Extramural%20Organization%3A,-A%20foreign%20or https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:~:text=Intramural%20DOW%20Organization%3A%20A%20subset%20of%20intragovernmental%20organizations%3B%20refers%20specifically%20to%20DOW%20organizations%2C%20including%20DOW%20laboratories%2C%20DOW%20military%20treatment%20facilities%2C%20and/or%20DOW%20activities%20embedded%20within%20a%20civilian%20medical%20center https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=APPENDIX%201-,RECIPIENT%20QUALIFICATION%20AND%20RESTRICTION%20INFORMATION,-A.%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0

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3. Program Description

The Defense Health Agency Contracting Activity (DHACA) is soliciting applications to this funding opportunity using delegated authority provided by United States Code, Title 10, Section 4001 (10 USC 4001). The CDMRP is the program office managing this FY26 funding opportunity as part of the Amyotrophic Lateral Sclerosis Research Program (ALSRP). The CDMRP is located within the Defense Health Agency Research and Development (DHA R&D), which is a part of the Department of Defense, DOD, herein referred to using the secondary title Department of War, DOW. Congress initiated the ALSRP in 2007 to provide support for research of high potential impact and exceptional scientific merit. Appropriations for the ALSRP from FY07 through FY25 totaled $309.4M. The FY26 appropriation is $40.0M.

The Vision of the FY26 ALSRP is to improve outcomes and find cures for people with ALS. The Mission is to fund and accelerate research that translates science into effective ALS treatments.

The program will prioritize applications that support the vision and mission of the FY26 ALSRP.

3.1. Award History

The ALSRP Clinical Outcomes and Biomarkers Award (COBA) mechanism was first offered in FY24. Since then, 58 Clinical Outcomes and Biomarkers Award applications were received, and 12 were recommended for funding.

3.2. Intent of the Clinical Outcomes and Biomarkers Award

The FY26 ALSRP COBA supports the development and/or validation of clinical outcomes and biomarkers to enrich clinical trials in ALS. Projects can be relevant to a specific therapy, a class of therapeutics, or to a specific ALS subtype (such as a particular genetic mutation) and do not have to broadly apply to all patients. Biomarkers should be specific for ALS, rather than generic. The FY26 ALSRP is particularly interested in studies that compare ALS-specific biomarkers to its mimics.

Research may include, but is not limited to:

• Target engagement biomarkers.

• Pharmacodynamic biomarkers to measure the biological effect of an investigational therapeutic.

• Predictive/cohort-selective biomarkers that indicate whether a specific therapy is likely to be effective in an individual patient or patient subgroup.

• Diagnostic, prognostic, phenotypic conversion, and/or disease progression biomarkers.

Diagnostic biomarkers that help distinguish ALS from other clinical mimics are of particular interest to the FY26 ALSRP.

• Clinician-, observer-, patient-reported, and/or performance outcomes to better support clinical trial success metrics.

• Defining ALS subtypes using patient-based resources, such as biosamples and/or digital data elements linked to rigorous molecular and clinical data.

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• Addition of the collection of biospecimens, outcome measures, or digital health data to an on-going or planned clinical trial.

• Correlation of clinical-trial related data (e.g., analysis of biosamples, imaging, and/or digital health data) with clinical outcomes or responses to therapies.

3.2.1. Key Elements for the COBA

Applications should address clinical biomarkers and/or clinical outcomes as described below:

Clinical Biomarkers: Identification, development, and/or validation of promising biomarkers for ALS. Biomarkers may include, but are not limited to susceptibility/risk, diagnostic, phenotypic conversion, monitoring/disease progression, prognostic, predictive, response, or safety biomarkers.

Clinical Outcomes: Identification, development, and/or validation of clinician-, observer-, or patient-reported, and/or performance outcome measures for ALS. Projects may include optimization of current outcome measures already in use.

Both clinical biomarkers and clinical outcomes research projects may utilize digital health measures, including wearable devices, smart-phone sensors, video or voice recordings, imaging studies, or other devices which record disease-relevant physiological data and/or outcomes.

Use of existing well-characterized and highly curated clinical resources is encouraged.

Examples of patient-based ALS resources include ongoing or completed clinical trial datasets, biorepositories of clinical specimens, registries (e.g., Centers for Disease Control and Prevention National ALS Registry and/or Biorepository, large omics datasets, patient-reported outcomes, digital biomarker datasets, and databases of clinical data and/or metadata. Active-duty military and/or Veteran patient populations or resources should be considered.

Collaboration with the DOW and/or U.S. Department of Veterans Affairs (VA) is also encouraged. A list of websites that may be useful in identifying additional information about ongoing DOW and VA areas of research interest or potential opportunities for collaboration can be found in Appendix 10 of the GAI. A list of suitable ALS-specific resources can be found on the ALSRP web page. Other resources used must include an adequate description of repository parameters and mechanisms for broad access.

A strong Data and Research Resources Sharing Plan is an important component for a successful COBA application.

Studies prospectively enrolling patients to collect biospecimens and/or clinical or digital data are permitted. The proposed studies may be stand-alone or add-on noninterventional clinical research studies. However, clinical trials are not allowed under this mechanism.

Employing community collaborations to optimize research impact: Research funded by the FY26 ALSRP COBA should be responsive to the needs of people with ALS, their families and/or their care partners. Pre-applications and applications are required to incorporate Community Collaboration to provide advice and consultation throughout the planning of the research project.

Applications investigating clinical outcomes, proposing prospective biospecimen collection, or enrolling patients must also integrate the community collaborator(s) in the implementation and execution of the research project.

The Community Collaboration partners should have meaningful and ongoing input on all aspects of projects that involve prospective recruitment, which can include needs assessment, https://www.cdc.gov/als/Default.html https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#DOW_AND_VA_WEBSITES https://cdmrp.health.mil/alsrp/resources/FY24%20ALSRP%20Research%20Resource%20database%2020240410.pdf

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FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 8 planning, research intervention design, implementation, evaluation and dissemination. These collaborations are expected to facilitate accessible, efficient and humane research approaches.

Interactions with other team members should be well-integrated and ongoing, and not limited to attending seminars and semi-annual meetings. Examples of Community Collaborations include (only one collaboration is required):

• Person(s) Living with ALS, Family Member(s) and/or Caregiver(s): The research team includes persons with ALS, their family members, or caregivers (past or present) as project advisors who will provide advice and consultation throughout the planning and implementation of the research project.

• Partnership with a Community-Based Organization: The research team establishes a partnership with at least one community-based organization that provides advice and consultation throughout the planning and implementation of the research project.

Community-based organizations may include advocacy groups, service providers, policymakers, or other formal organizational stakeholders.

• Community Advisory Board: A community advisory board is composed of multiple community stakeholders and can take many forms, from a board of people living with ALS, their family members, or caregivers to a coalition of community-based organizations, or any combination thereof. As with people living with ALS and organizational partners, the community advisory board provides advice and consultation throughout planning and implementation of the research project.

For projects proposing the use of large datasets for training predictive models, a discussion of mechanisms for addressing rigor in model design, training and assessment should be provided.

Depending upon the context, this might include algorithmic designs to avoid overfitting, saliency analysis, feature attribution, node ablation or other alternate strategies.

A description of the biomarker category and intended context of use (COU), including regulatory considerations for use in ALS clinical trials or clinical practice, is an important component. For further information on biomarker types, qualifications, and use in ALS clinical trials, it is recommended that applicants consult the following resources:

• “National Institute of Neurological Disorders and Stroke (NINDS) Biomarker Program,” National Institutes of Health (NIH) https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research.

• “U.S. Food and Drug Administration (FDA) Biomarker Qualification Program,” FDA, https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program.

• FDA-NIH Biomarker Working Group, BEST (Biomarkers, EndpointS, and other Tools) Resource (U.S. Food and Drug Administration, 2016+), https://www.ncbi.nlm.nih.gov/books/NBK326791/.

• FDA Center for Drug Evaluation and Research, Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry (FDA, 2019), https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry.

• Leonard H van den Berg et al, “Revised Airlie House Consensus Guidelines for Design and Implementation of ALS Clinical Trials,” Neurology 92, no. 14 (2019): e1610-e1623, https://pubmed.ncbi.nlm.nih.gov/30850440/.

https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research https://www.ninds.nih.gov/current-research/focus-tools-topics/focus-biomarkers-research https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program https://www.fda.gov/drugs/drug-development-tool-ddt-qualification-programs/biomarker-qualification-program https://www.ncbi.nlm.nih.gov/books/NBK326791/ https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://www.fda.gov/regulatory-information/search-fda-guidance-documents/amyotrophic-lateral-sclerosis-developing-drugs-treatment-guidance-industry https://pubmed.ncbi.nlm.nih.gov/30850440/

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FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 9

• Nick S. Verber et al, “Biomarkers in Motor Neuron Disease: A State of the Art Review,” Frontiers in Neurology 10 (2019): 291, https://www.frontiersin.org/articles/10.3389/fneur.2019.00291/full.

• Michael Benatar et al, “ALS Biomarkers for Therapy Development: State of the Field and Future Directions,” Muscle Nerve 53, no. 2 (2016): 169-182, https://doi.org/10.1002/mus.24979.

For further information on digital health guidance guidelines, it is recommended that applicants consult the following resources:

• Caroline Franck Perrin et al, “iCHECK-DH: Guidelines and Checklist for the Reporting on Digital Health Implementations,” Journal of Medical Internet Research 25 (2023): e46694, https://doi.org/10.2196/46694.

• Srikanth Vasudevan et al, “Digital Biomarkers: Convergence of Digital Health Technologies and Biomarkers,” NPJ Digital Medicine 5, no. 1 (2022): 36, https://doi.org/10.1038/s41746-

022-00583-z.

3.2.2. Other Important Considerations for the COBA

The ALSRP aims to improve the health, care, and well-being of military Service Members, Veterans, their Families, and the American public affected by ALS. Evidence from scientific research suggests a mutually inclusive relationship between ALS and military service, with a higher rate of incidence in the Veteran population, without any known reason(s) for this incidence. Knowledge, information, products or technologies gained from the proposed research should advance research that is of significance to Service Members, Veterans and/or their Families.

In accordance with the National Defense Authorization Act for Fiscal Year 2026, Section 732, the CDMRP does not support the conduct of painful research (U.S. Department of Agriculture pain category D or E) involving domestic cats or dogs, except for studies relating to military or service animals.

Clinical trials are not allowed within this funding opportunity.

All projects should adhere to a core set of standards for rigorous study design and reporting to maximize the reproducibility and translational potential of clinical and preclinical research, such as those described in the STROBE, CONSORT, SPIRIT and ARRIVE 2.0 guidelines.

Applications from investigators within the DOW and applications involving multidisciplinary collaborations among academia, industry, the DOW, the VA and other federal government agencies are highly encouraged. These relationships can leverage knowledge, infrastructure and access to unique clinical populations that the collaborators bring to the research effort, ultimately advancing research that is of significance to Service Members, Veterans, their Families and the American public. If the proposed research relies on access to unique resources or databases, the application must describe the access at the time of submission and include a plan for maintaining access as needed throughout the proposed research.

3.3. Funding Instrument

The funding instrument for awards made under the program announcement will be grants

(31 USC 6304).

https://www.frontiersin.org/articles/10.3389/fneur.2019.00291/full https://doi.org/10.1002/mus.24979 https://doi.org/10.2196/46694 https://doi.org/10.1038/s41746-022-00583-z https://doi.org/10.1038/s41746-022-00583-z https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Definition_List:~:text=or%20hardware%20procurement.-,Clinical%20Trial%3A,-As%20defined%20in https://www.strobe-statement.org/ https://www.nature.com/articles/s41591-025-03635-5#:~:text=SPIRIT%20and%20CONSORT%20are%20evidence,relevant%20empirical%20evidence%20where%20possible https://www.nature.com/articles/s41591-025-03668-w?fromPaywallRec=false https://arriveguidelines.org/arrive-guidelines

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3.4. Funding Details

Period of Performance: The maximum period of performance is three years.

Cost Cap: The application’s total costs budgeted for the entire period of performance should not exceed $1.0M. If indirect cost rates have been negotiated, indirect costs are to be budgeted in accordance with the organization’s negotiated rate. Collaborating organizations should budget associated indirect costs in accordance with each organization’s negotiated rate.

All direct and indirect costs of any subaward or contract must be included in the direct costs of the primary award.

The applicant may request the entire maximum funding amount for a project that may have a period of performance less than the maximum three years.

The appropriateness of the budget for the proposed research will be assessed during peer review.

Direct Cost Restrictions: For this award mechanism, direct costs:

May be requested for (not all-inclusive):

• Travel in support of multi-institutional collaborations.

• Costs for one investigator to travel to two scientific/technical meetings per year. The intent of travel to scientific/technical meetings should be to present project information or disseminate project results from the ALSRP Clinical Outcomes and Biomarkers Award.

Must not be requested for:

• Costs for travel to scientific/technical meeting(s) beyond the limits stated above.

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4. Application Contents and Format

4.1. Application Overview

Application submission is a two-step process requiring both a pre-application submitted via the Electronic Biomedical Research Application Portal (eBRAP) and a full application submitted through eBRAP or Grants.gov. Depending on the submission portal, certain aspects of the application will differ.

Intramural DOW organizations submitting a full application should follow instructions for submission through eBRAP.

Extramural organizations submitting a full application must follow instructions for submission through Grants.gov.

4.2. Pre-Application Components

Pre-application submissions must include the following components.

Upload documents as individual PDF files unless otherwise noted. Files must comply with the formatting guidelines listed in the GAI.

• Preproposal Narrative (three-page limit): The Preproposal Narrative page limit applies to text and non-text elements (e.g., figures, tables, graphs, photographs, diagrams, chemical structures, drawings) used to describe the project. Inclusion of URLs that provide additional information to expand the Preproposal Narrative and could confer an unfair competitive advantage is prohibited and may result in administrative withdrawal of the pre-application.

The Preproposal Narrative should include the following:

○ Use of Clinical ALS Resources: Summarize how the project will prospectively collect clinical samples/data or will leverage existing ALS repositories and/or datasets.

○ Biomarker Development: Describe the biomarker category and intended COU in ALS therapy development, including regulatory considerations for use in ALS clinical trials or clinical practice. Reference the FDA Biomarker Qualification Program for COU definitions and examples. Concisely state the project’s hypothesis, specific aims, and feasibility of the scientific approach. Provide scientific rationale of how the research will support the project objectives or hypothesis, specific aims, and feasibility.

○ Data Sharing: Describe plans to make results or outcomes available for use by others.

Include considerations of existing, publicly available and curated ALS repositories.

○ Clinical Impact in the Intended Population: Explain how the proposed project will advance the development and/or validation of biomarkers for disease progression or prognosis assessment; or how the project is relevant to a specific therapeutic (or class of therapeutics) or to a specific type of ALS (such as a particular genetic mutation) with potential to better define subsets. Identify community collaboration partner(s), and describe how they will provide advice and consultation throughout the planning and implementation of the research project.

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• Pre-Application Supporting Documentation: The items to be included as supporting documentation for the pre-application must be uploaded as individual files and are limited to the following:

○ References Cited (one-page limit): List the references cited (including URLs if available) in the Preproposal Narrative using a standard reference format for the full citation (i.e., author[s], year published, reference title, and reference source, including volume, chapter, page numbers, and publisher, as appropriate).

○ List of Abbreviations, Acronyms, and Symbols: Provide a list of abbreviations, acronyms, and symbols used in the Preproposal Narrative.

○ Key Personnel Biographical Sketches: All biographical sketches should be uploaded as a single combined file. Biographical sketches should be used to demonstrate background and expertise through education, positions, publications, and previous work accomplished.

4.3. Full Application Components

Applicants must receive an invitation to submit a full application. Uninvited full application submissions will be rejected.

Each application submission must include the completed full application package for this program announcement. See Appendix 1 for a checklist of the full application components.

(a) SF424 Research & Related Application for Federal Assistance Form (Grants.gov submissions only):

IMPORTANT: When completing the SF424 R&R, enter the eBRAP log number assigned during pre-application submission into Block 4a – Federal Identifier.

(b) Attachments:

Each attachment of the full application components must be uploaded as an individual file in the format specified and in accordance with the formatting guidelines in the GAI.

○ Attachment 1: Project Narrative (12-page limit): Upload as “ProjectNarrative.pdf”.

Describe the proposed project in detail using the outline below.

– Background and Scientific Rationale: Explain why the proposed research is important and how it addresses clinical biomarkers and/or clinical outcomes.

Describe the scientific rationale on which the proposed work is based. Demonstrate feasibility as demonstrated by a critical review and analysis of published literature, logical reasoning and presentation of published or unpublished preliminary data.

Preliminary data should be clearly described with statistics. Strong rationale and feasibility, showing proof of concept and clinical relevance of the proposed research, are critical.

– Study Personnel Description: Describe the composition of the study team in enough detail to determine whether the team includes relevant subject matter expertise to accomplish the proposed work. Include the roles of individuals named in the organizational chart along with any external consultants or advisors who will provide critical guidance and input to the study team (e.g., statistician, regulatory expert, community collaborator). Inclusion of a biomarker interpretation expert is highly encouraged.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=APPENDIX%202.%0AFORMATTING%20GUIDELINES https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=(a)%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%C2%A0%20SF424%20(R%26R)%20%E2%80%93%20Application%20for%20Federal%20Assistance%20Form https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Project%20Narrative%3A,-Attach%20as%20%E2%80%9CProjectNarrative https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Content_Form_Full_App_Submission:~:text=eBRAP%20User%20Name-,Biographical%20Sketch,-%3A%20This%20file

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Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 13

– For Clinical Outcome Studies: Describe the clinician-, observer-, or patient-reported outcome with respect to ALS biology or clinical relevance. Describe how easily this outcome may be incorporated into future clinical trials of a proposed therapeutic.

– For Clinical Biomarker Studies: Describe feasibility of the biomarker with respect to ALS biology or clinical relevance. Clearly describe the biomarker category and intended COU in ALS therapy development, including regulatory considerations for use in ALS clinical trials or clinical practice. Reference the FDA Biomarker Qualification Program for COU definitions and examples. Describe how the proposed study has the potential to lead to major advancements in ALS treatment or to better define subsets for clinical treatment. The inclusion of a decision-tree diagram that explicitly illustrates the application of the biomarkers and includes the anticipated actions to be taken based on the biomarker results is recommended. Describe how easily and reliably the biomarkers may be implemented in eventual clinical trials of a proposed novel therapeutic.

– Research Strategy and Specific Aims: Describe the experimental design, methods, and statistical plan and analyses, including appropriate controls and endpoints, in sufficient detail. The statistical plan should be appropriate for the variables being measured. A biostatistician may be recruited to peer review the application.

▪ Describe the type of ALS patient specimen, patient data and/or existing cohort being leveraged and explain how the resource is appropriate for the objectives of the study.

▪ Provide statistical considerations to demonstrate that the work is appropriately powered.

▪ Applications involving artificial intelligence should include details regarding the specific platforms and approaches they intend to implement.

▪ If recruiting human subjects for patient specimen collection, describe the study population and include a detailed plan for recruitment provided additional details in Attachment 12). This award may not be used to conduct clinical trials.

▪ Describe whether the population selected to participate in the study stands to benefit from the knowledge to be gained as a result of the proposed research, how the level of risk to study participants is minimized, and what safety monitoring and reporting measures are taken for the level of risk.

▪ Concisely explain the project’s specific aims to be funded by this award. Describe how data will be collected, handled, and analyzed (including a detailed statistical plan) in a manner consistent with the study objectives.

▪ Briefly describe plans to make results or outcomes available for use by others.

Details of data and resource sharing should be provided in Attachment 10, Data and Research Resources Sharing Plan.

▪ Consult appropriate guidelines to ensure relevant aspects of rigorous and reproducible research are adequately planned for and, ultimately, reported.

▪ Describe potential challenges and alternative strategies where appropriate.

If the proposed research involves access to military and/or VA patient populations and/or DOW or VA resources or databases, describe the access at the time of submission and https://www.fda.gov/drugs/biomarker-qualification-program/context-use https://www.fda.gov/drugs/biomarker-qualification-program/context-use

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FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 14 include a plan for maintaining access as needed throughout the proposed research.

Also, include a plan for obtaining any required data sharing, memorandum of understanding, or other agreements required to access and publish data. Refer to the GAI, Appendix 4, for additional considerations.

○ Attachment 2: Supporting Documentation: Combine and upload as a single file named “Support.pdf”.

There are no page limits for these components unless otherwise noted. Include only components described below; inclusion of items not requested or viewed as an extension of the Project Narrative will result in the removal of those items or may result in administrative withdrawal of the application.

References Cited: List the references cited in the Project Narrative using a standard reference format (include URLs, if available).

List of Abbreviations, Acronyms and Symbols: Provide a list of abbreviations, acronyms and symbols.

Facilities, Existing Equipment and Other Resources: Describe the facilities and equipment available for performance of the proposed project; include any additional facilities or equipment proposed for acquisition at no cost to the award. Indicate whether government-furnished facilities or equipment are proposed for use. If so, reference the original or present government award under which the facilities or equipment items are now accountable. There is not a standardized form for this information.

Publications and/or Patents: Include a list of relevant publication URLs and/or patent abstracts. If articles are not publicly available, then copies of up to five published manuscripts may be included in Attachment 2. Extra items will not be reviewed.

Letters of Support (two-page limit per letter is recommended): Provide individual letters signed by collaborating individuals and/or organizational officials demonstrating that the PI has the support and resources necessary for the proposed work. Letters from the PI’s Department Chair, or appropriate organization official, should also confirm that the PI(s) meet eligibility criteria. If applicable, provide a letter of support, signed by the lowest-ranking person with approval authority, confirming participation of intramural DOW collaborator(s) and/or access to military populations, databases or DOW resources. If applicable, provide a letter of support signed by the VA Facility Director(s), or an individual designated by the VA Facility Director(s), confirming access to VA patients, resources and/or VA research space.

Sex as a Biological Variable Strategy (two-page limit is recommended):

Describe the strategy for how sex will be considered as a biological variable. This strategy should include a brief discussion of what is currently known regarding sex differences in the applicable research area. Clearly articulate how sex as a biological variable will be factored into the data analysis plan and how data will be collected and disaggregated by sex. If needed, provide a strong rationale for proposing a single-sex study, based on justification from scientific literature, preliminary data or other relevant considerations. Refer to the CDMRP Directive on Sex as a Biological Variable in Research for additional information.

https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Use_Of_DOW_Dept_Veterans_Affairs_Resource:~:text=APPENDIX%204.%0AUSE%20OF%20DOW%20OR%20U.S.%20DEPARTMENT%20OF%20VETERANS%20AFFAIRS%20RESOURCES https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://cdmrp.health.mil/pubs/pdf/CDMRP%20SABV%20Directive_Revised_MAR2025_signed.pdf https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Supporting%20Documentation%3A,-Combine%20and%20attach

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FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 15

○ Attachment 3: Technical Abstract (one-page limit): Upload as “TechAbs.pdf”.

Write the technical abstract using the outline below. Clarity and completeness within the space limits are highly important.

Background: Present the scientific rationale behind the proposed research project.

Clearly define the goals of the effort/study.

Hypothesis/Objective(s): State the hypothesis to be tested and/or objective(s) to be reached.

Specific Aims: State the specific aims of the study.

Study Design: Describe the study design, including appropriate controls.

Impact: Explain how the proposed project has the potential to lead to critical discoveries or major advancements in clinical outcomes, disease progression markers for a specific therapeutic or class of therapeutics or for a specific type of ALS (such as a particular genetic mutation) to better define subsets.

Relevance to Military Health: Briefly describe how the proposed research is relevant to Service Members, Veterans and their Families.

○ Attachment 4: Lay Abstract (one-page limit): Upload as “LayAbs.pdf”.

The lay abstract should address the points outlined below in a manner that is readily understood by readers without a background in science or medicine. Avoid overuse of scientific jargon, acronyms and abbreviations. Do not duplicate the technical abstract.

– Summarize the goals, objectives and rationale for the proposed research.

– What type(s) of ALS patients will the research help and how will it help them?

– What are the potential clinical applications, benefits and risks of the anticipated outcomes?

– What is the projected time it may take to achieve a patient-related outcome?

– What are the likely contributions of this study to improve treatments and find cures for ALS?

– What is the potential benefit of the proposed study and the anticipated outcomes to

Service Members, Veterans and/or their Families?

○ Attachment 5: Statement of Work (three-page limit): Upload as “SOW.pdf”.

Refer to eBRAP for the Suggested SOW Format.

For guidance on preparing the SOW, refer to either the Example: Assembling a Clinical Research and/or Clinical Trial Statement of Work or Example: Assembling a Generic Statement of Work, whichever is most appropriate for the proposed effort. Include milestones for data or research resource(s) sharing.

○ Attachment 6: Letter(s) Confirming Access to Population(s) or ALS Patient Resource(s), if applicable (one-page limit per letter is recommended): Upload as “Access.pdf”. Provide a letter of support signed by the appropriate institution official who has the authority to confirm access to the proposed population(s) or resource(s) necessary to carry out the study. Resources include, but are not limited to, patient biosamples, clinical data, existing cohorts or other components of current clinical care.

https://ebrap.org/eBRAP/public/Program.htm#:~:text=Suggested%20SOW%20Format https://ebrap.org/eBRAP/public/Program.htm#:~:text=Example%3A%20Assembling%20a%20Clinical%20Research%20and/or%20Clinical%20Trial%20Statement%20of%20Work https://ebrap.org/eBRAP/public/Program.htm#:~:text=Example%3A%20Assembling%20a%20Clinical%20Research%20and/or%20Clinical%20Trial%20Statement%20of%20Work https://ebrap.org/eBRAP/public/Program.htm#:~:text=Example%3A%20Assembling%20a%20Generic%20Statement%20of%20Work https://ebrap.org/eBRAP/public/Program.htm#:~:text=Example%3A%20Assembling%20a%20Generic%20Statement%20of%20Work https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Lay%20Abstract%3A,-Attach%20as%20%E2%80%9CLayAbs https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Technical%20Abstract%3A,-Attach%20as%20%E2%80%9CTechAbs https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01#_Recipient_Qualification_Restriction_Info:~:text=%C2%B7-,Statement%20of%20Work%3A,-Attach%20as%20%E2%80%9CSOW

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FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 16

○ Attachment 7: Clinical Impact Statement (one-page limit): Upload as “Impact.pdf”.

Describe how the proposed work will impact ALS clinical care. The statement should address the points outlined below written in a manner that is readily understood by readers without a background in science or medicine. Specifically highlight how the clinical biomarker development and/or validation effort will:

Advance the development of biomarkers for disease progression, phenotypic conversion detection, or prognosis assessment; or is relevant to a specific therapeutic (or class of therapeutics) or to a specific type of ALS (such as a particular genetic mutation) with potential to better define subsets.

Lead to meaningful improvements in patient care.

Create new and outstanding shared resources and/or enhance the value of existing research resources through biosamples, data, and information sharing.

Describe how knowledge, information, products or technologies gained from the proposed research advance research that is of significance to Service Members, Veterans and/or their Families.

– If applicable, describe the short-term or long-term potential for significant reduction or elimination of the disproportionate effects of ALS on specific populations.

– If applicable, describe how the anticipated outcomes of the proposed study will make an impact in understanding health differences between sexes.

Key points may be bulleted to emphasize the main study goals. Inclusion of a simple diagram of the proposed study, if plausible, is encouraged.

○ Attachment 8: Community Collaboration Plan (no page limit): Upload as “Community.pdf”. Refer to Section 3.2.2 for more details regarding the Community collaboration requirement. This attachment must be written in a manner that will be readily understood by readers without a background in science or medicine.

Community Collaboration Statement: Describe the collaborative research approach that will be used (e.g., lived experience consultant or a partnership with community-based organization or a community advisory board). Detail when and how the approach will be used within the research project; how the community collaborator(s) will be engaged throughout the study; how input will be meaningfully incorporated into the research design, execution, and dissemination; and explain how this best serves the ALS community.

Include the name of at least one community partner—person(s) with ALS, family member(s) and/or care partner(s), representative of a community-based organization or community advisory board—who will provide advice and consultation throughout the planning and implementation of the research project.

Describe any training, co-learning, or capacity-building activities that will be provided to both scientific researchers and community partners on collaborative research approaches, decision-making and equitable participation.

Letters of Community Collaboration (two-page limit per letter is recommended): Provide a letter signed by each community collaborator confirming their role and commitment to participate on the research team and throughout the research effort. The letter should include a mention of why the qualifications and/or background of the individual will benefit the proposed research project. If a community-based organization/advisory board will be engaged, the letter of

Basic Information | Eligibility | Program Description | Application Contents and Format | Submission Requirements

Application Review Information | Federal Award Notices | Post-Award Requirements | Other Information

FY26 Amyotrophic Lateral Sclerosis Clinical Outcomes and Biomarkers Award 17 commitment should be signed by BOTH the organization point of contact and the organization’s leadership endorsing the collaboration.

Describe how feedback from the ALS community will be integrated into the progression of this research and continued development of the intervention.

○ Attachment 9:…