HT942526PRMRPCTA_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

Peer Reviewed Medical Research Program

Clinical Trial Award

Funding Opportunity Number: HT942526PRMRPCTA

Pre-Application Due: July 23, 2026

Application Due: September 22, 2026 https://ebrap.org/eBRAP/public/gai.htm?version=CD26_01

FY26 Peer Reviewed Medical Clinical Trial 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 Trial 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

Appendix 3 Application Category Summary

FY26 Peer Reviewed Medical Clinical Trial Award 3

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

FY26 Peer Reviewed Medical Clinical Trial Award 4

1. Basic Information About the Funding Opportunity

Summary: The fiscal year 2026 (FY26) Peer Reviewed Medical Research Program (PRMRP) Clinical Trial Award supports the rapid implementation of clinical trials with the potential to have significant impact on the treatment and management of a disease or condition addressed in one of the congressionally directed FY26 PRMRP topic areas and FY26 PRMRP strategic goals.

Distinctive Features: Must support a clinical trial. Supports two different application categories, based on the phase of planning for the clinical trial: Clinical Trial Only or Clinical Trial with Planning Phase. The Clinical Trial with Planning Phase option is intended to support the final phase of regulatory activities and planning activities that are necessary to be completed prior to initiation of the clinical trial. The planning phase cannot be used to finalize the intervention or support animal studies. Applications that already have regulatory approvals in place and are submitting to the Clinical Trial Only option may be prioritized over those requesting the Planning Phase option. Animal studies are not supported. Studies must complete all preclinical empirical laboratory work prior to the award start date.

• Supports three funding levels, each offered with and without a Planning Phase:

○ Funding Level 1: Supports phase 0 or phase 1 clinical trials or non-phased trials with fewer than 100 participants.

○ Funding Level 2: Supports phase 2 clinical trials or non-phased trials with fewer than 300 participants.

○ Funding Level 3: Supports phase 3 clinical trials or non-phased trials with more than 300 participants.

Funding Details: The Congressionally Directed Medical Research Programs (CDMRP) expects to allot roughly $94.5M to fund approximately 9 Clinical Trial Award applications with total cost caps of $800,000 for the planning phase of a Clinical Trial with Planning Phase, $6M for Funding Level 1, $10M for Funding Level 2, and $20M for Funding Level 3 per award. The maximum period of performance is 4 years for the clinical trial, and 12 months for the planning phase. 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), July 23, 2026

• Invitation to Submit an Application: August 24, 2026

• Application Submission Deadline: 11:59 p.m. ET, September 22, 2026

• End of Application Verification Period: 5:00 p.m. ET, September 30, 2026

• Peer Review: November/December 2026

• Programmatic Review: February/March 2027

Announcement Type: Initial

Funding Opportunity Number: HT942526PRMRPCTA

Assistance Listing Number: 12.420

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

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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 (e.g., Assistant Professor, Senior Scientist, Principal Scientist, Research Director, or equivalent) may be named by the organization as the Principal Investigator (PI) on the application.

Each investigator may be named on only one FY26 PRMRP application as PI. If more than one pre-application submitted to the FY26 PRMRP names the same PI, the first submission will be accepted, and subsequent submissions will be administratively withdrawn.

Independent investigators affiliated with an eligible organization are eligible to be named as PI on the application, regardless of ethnicity, nationality or citizenship status.

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#_Definition_List:~:text=Extramural%20Organization%3A,and%20research%20institutes.

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.%0ARECIPIENT%20QUALIFICATION%20AND%20RESTRICTION%20INFORMATION

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

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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 Peer Reviewed Medical Research Program (PRMRP). 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 PRMRP in 1999 to support medical research projects of clear scientific merit and direct relevance to military health. Appropriations for the PRMRP from FY99 through FY25 totaled $4.34 billion. The FY26 appropriation is $370 million.

FY26 PRMRP Research Development Pipeline

To address the congressionally directed FY26 PRMRP topic areas in a bench-to-bedside fashion, the FY26 PRMRP award mechanisms are aligned to different phases of the research development pipeline illustrated below.

The Use-Inspired Basic Research phase represents novel, exploratory research aimed at generating preliminary data and/or preclinical research that is ready for validation through expansion, replication, or comparative studies. While projects may be aiming to understand fundamental physiological phenomena, “basic research,” they should be driven by a specific clinical need and potential application, “use-inspired.” Applicants seeking support for research aligning to the Use-Inspired Basic Research phase may consider:

• FY26 PRMRP Discovery Award (HT942526PRMRPDA) for novel, high-risk, high reward research projects with the potential to yield high-impact findings and new avenues of investigation. Preliminary data is not allowed.

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• FY26 PRMRP Research Advancement Award (HT942526PRMRPRAA) for building upon existing preliminary data to validate a concept.

The Translational Research phase seeks to transition scientific data towards treatment, diagnostic and/or preventive strategies. Research projects are expected to have significant near-term impact on patients’ lives. Examples of projects in the translational phase include product/device development and clinical translation of concepts previously validated through expansion, replication or comparative studies. Applicants seeking support for research aligning to the Translational Research phase may consider:

• FY26 PRMRP Impact Award (HT942526PRMRPIPA) for mature research projects that are ready to translate ideas into solutions. Initial product discovery, development, and optimization are supported.

• FY26 PRMRP Technology/Therapeutic Development Award (HT942526PRMRPTTDA) for finalizing preclinical development of tangible products (drugs or biologics), knowledge-based products and/or devices. The research outcome should be a regulatory filing or translation of findings into clinical practice, as applicable.

The Translational to Clinical Transition phase represents the final stages of product development with early, phase 0/1, or equivalent, clinical trials. Products may include both knowledge and tangible items that will be used to impact patient care.

• FY26 PRMRP Platform Clinical Translation Award (HT942526PRMRPPCTA) for finalizing preclinical development, conducting clinical validation studies, and/or conducting first in human clinical trials for a platform product with the potential to impact clinical care for two or more FY26 PRMRP topic areas.

The Clinical Research phase represents small- and large-scale confirmatory trials and/or applied clinical research that will revolutionize the clinical management of the diseases and conditions assigned to the program as topic areas. Applicants seeking support for trials and studies aligned to the Clinical Research phase may consider:

• FY26 PRMRP Lifestyle and Applied Health Research Award (HT942526PRMRPLAHRA) for clinical trials focused on efficacy of non-pharmacological interventions or noninvasive devices or clinical research to examine the impact of prevention, diagnostic, treatment or health care delivery approaches on health outcomes. Animal research is not allowed.

• FY26 PRMRP Clinical Trial Award (HT942526PRMRPCTA) for projects to determine the safety or efficacy outcomes of pharmacological interventions, devices or implants on prospectively recruited human participants. Animal research, preclinical experiments, and optimization/validation of the intervention are not allowed.

NOTE: The scope of research proposed in applications in response to the FY26 PRMRP program announcements must align with the research phases outlined above. It is the responsibility of the applicant to select the award mechanism that aligns with the scope of the proposed research. The funding mechanism should be selected based on the research scope defined in the program announcement, and not on the amount of the budget. Applications submitted under a mechanism that is not deemed appropriate for the scope of research proposed will not be funded.

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3.1. Award History

The PRMRP first offered the Clinical Trial Award mechanism in FY08. In FY20, the PRMRP introduced the planning phase option to the Clinical Trial Award. The PRMRP offers multiple funding levels supporting specifical clinical trial phases for the first time in FY26.

3.2. Intent of the Clinical Trial Award

The PRMRP Clinical Trial Award (CTA) mechanism supports the rapid execution and analysis of clinical trials with the potential to have a significant impact on the treatment or management of a disease or condition addressed in one of the congressionally directed FY26 PRMRP Topic Areas and FY26 PRMRP Strategic Goals. Clinical trials may be designed to evaluate promising new products, pharmacologic agents (drugs, biologics or medical devices), clinical guidance, and/or emerging approaches and technologies. Proposed projects may range from small proof-of-concept trials (i.e., pilot, first-in-human, phase 0) that demonstrate the feasibility or inform the design of more advanced trials through to large-scale trials, including comparative effectiveness trials that will transform and revolutionize care for the diseases and conditions addressed in the congressionally directed FY26 PRMRP Topic Areas.

Apply the following four questions to determine whether the PRMRP would consider a research study to be a clinical trial:

• Does the study involve human participants?

• Are the participants prospectively assigned to an intervention?

• Is the study designed to evaluate the effect of the intervention on the participants?

• Is the effect being evaluated a health-related biomedical or behavioral outcome?

If the answer to all four questions is “yes,” then the clinical study would be considered a clinical trial.

The PRMRP CTA is intended to have near-term impact on clinical care. Proposed interventions must be intended to change the health status of the participants. Studies that meet the definition of a clinical trial but are designed to understand a basic physiological phenomenon should consider one of the other FY26 PRMRP program announcements that allows for both clinical research and trials. Additionally, animal studies are NOT allowed under this award mechanism.

All preclinical empirical laboratory work must be completed prior to the award start date.

Applicants seeking funding for research that does not meet the above definition for a clinical trial or does not otherwise meet the intent of this mechanism should consider one of the other FY26 PRMRP program announcements being offered. For information about these award mechanisms, see the FY26 PRMRP Research Development Pipeline.

Two different application categories, based on the phase of planning for the clinical trial, are available under this program announcement (summary available in Appendix 3):

(1) Clinical Trial With Planning Phase: Intended to support the final phase of regulatory activities necessary to initiate the planned clinical trial. The proposed clinical trial must address one of the congressionally directed FY26 PRMRP Topic Areas and one of the FY26 PRMRP Strategic Goals. Funding of the clinical trial will be considered an optional research effort that is contingent upon meeting the milestones of the planning phase.

Patient enrollment for the clinical trial is expected to begin within three months after PRMRP exercises the option for the clinical trial.

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○ The planning phase should be limited to the activities that are necessary to be completed prior to the initiation of the clinical trial. Allowable tasks under the planning phase may include, but are not limited to, the following:

Planning for and obtaining appropriate regulatory approvals (for example, U.S. Food and Drug Administration (FDA) or equivalent international regulatory agency, Investigational New Drug [IND] or Investigational Device Exemption [IDE] submissions, Institutional Review Board [IRB] submissions, exception to informed consent and DOW Office of Human Research Oversight [OHRO] submissions)

Developing the clinical protocol

Developing training procedures

Establishing access to appropriate patient populations or resources

○ Within the maximum 12-month period of performance of the planning phase, recipients must submit an IND or IDE application to the FDA, if required, and obtain a statement that the IND or IDE is active/safe to proceed. If the clinical trial will be conducted at international sites, equivalent requirements for the host country(ies) must be met during the planning phase. Regulatory Agency approval or exemption to proceed with the clinical trial must be obtained, if applicable, before the optional clinical trial effort may be funded. The PRMRP will not exercise the option for the initiation of the proposed clinical trial if any of the following milestones are not met (for additional details, refer to Attachment 1: Project Narrative):

– A copy of the FDA acknowledgment letter, to include submission date and receipt date, and a statement that the FDA did not raise concerns and/or did not place the clinical trial on hold, or

– A copy of the FDA acknowledgment letter and meeting minutes (pre-IND/pre-IDE and/or Type C) that ascertain the FDA’s concurrence with the proposed regulatory approach if a technical or a protocol amendment to an active IND/IDE is necessary to complete the clinical trial, or

– A copy of the relevant national regulatory agency approval if the clinical trial will be conducted at an international site(s), or

– Evidence in writing from the IRB of record, or the FDA, that the proposed investigational drug/agent/device is exempt, or the proposed investigational device qualifies for an abbreviated IDE.

○ Human participants research is not allowed under the planning phase.

○ The planning phase is intended to be for projects truly requiring this time to mitigate risk of not being able to obtain the necessary regulatory approvals to proceed with the proposed clinical trial. The government reserves the right to switch applications to the Clinical Trial Only option if the planning phase is not needed for this purpose.

○ Research milestones to be accomplished by the end of the planning phase must be clearly defined in the project Statement of Work (SOW) and will be finalized during negotiations. The PI will be required to present an update on progress toward accomplishing research milestones and goals of the project at a Milestone Meeting, to be held virtually, at the discretion of the government. Milestone Meetings will be held nearing the conclusion of the planning phase and will be attended by members of the PRMRP Programmatic Panel, CDMRP staff, and the DHACA Grants Officer.

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○ The agreement to support the clinical trial option will be contingent upon (1) all necessary regulatory approvals obtained under the base award; (2) availability of funds;

and (3) accomplishment of research milestones and goals as determined by the PRMRP Programmatic Panel and DHACA Grants Officer.

(2) Clinical Trial Only: Intended to support clinical trials having Regulatory Agency approval or exemption at the time of application submission. The proposed clinical trial must address one of the congressionally directed FY26 PRMRP Topic Areas and one of the FY26 PRMRP Strategic Goals. Patient recruitment for the clinical trial is expected to begin no later than 9 months after the award date.

○ If the proposed clinical trial involves the use of a drug that has not been approved by the relevant Regulatory Agency for the country where the research will be conducted, then submission of an IND application, or equivalent, that meets all requirements under 21 CFR 312 may be required. It is the responsibility of the applicant to provide evidence from the IRB of record or the relevant Regulatory Agency if an IND, or equivalent, is not required. If an IND, or equivalent, is required, the regulatory application must be submitted to the relevant regulatory agency by the FY26 PRMRP CTA full application submission deadline. The IND, or equivalent, should be specific for the product and indication to be tested in the proposed clinical trial. For more information on IND applications specifically, review the FDA guidance. If the investigational product is a device, then submission of an IDE, or equivalent, application that meets all requirements under 21 CFR 812 may be required. It is the responsibility of the applicant to provide evidence if an IDE, or equivalent, is not required. If an IDE, or equivalent, is required, the IDE application, or equivalent, must be submitted to the relevant Regulatory Agency by the FY26 PRMRP CTA full application submission deadline. The IDE, or equivalent, should be specific for the device and indication to be tested in the proposed clinical trial.

○ If amendments to the IND/IDE, or equivalent, are needed before the proposed trial can begin, these must be submitted prior to the FY26 PRMRP CTA full application submission deadline.

○ Research milestones to be accomplished throughout each phase of the clinical trial must be clearly defined in the project SOW and will be finalized during negotiations. The government reserves the right to fund the clinical trial under a base award and subsequent optional research phases. Continued funding of the clinical trial and approval of research options will be contingent upon meeting mutually agreed upon milestones and goals as determined by the DHACA Grants Officer.

○ Refer to Attachment 8, Regulatory Strategy, for additional details on documents of regulatory submissions. The government reserves the right to withdraw applications submission under the Clinical Trial Only option if an active IND or IDE, IND or IDE amendment, or equivalent, is required but has not been submitted prior to the full application submission deadline and is not approved prior to the proposed award start date.

The FY26 PRMRP CTA offers three different funding levels with or without the Planning Phase.

Each funding level describes a defined clinical trial scope:

○ Funding Level 1: Supports phase 0 or phase 1 clinical trials or non-phased trials with fewer than 100 participants.

○ Funding Level 2: Supports phase 2 clinical trials or non-phased trials with fewer than 300 participants.

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○ Funding Level 3: Support phase 3 clinical trials or non-phased trials with more than 300 participants.

Applicants may request a funding level outside of the specified phase or participant requirements by submitting additional justification for the budget in both the pre-application and the full application (see Attachment 12, Funding Level Justification).

3.2.1. FY26 PRMRP Topic Areas and Strategic Goals

To meet the intent of the funding opportunity, all applications for FY26 PRMRP funding must specifically address one of the FY26 PRMRP topic areas as directed by the U.S. Congress and have direct relevance to military health. Additionally, the PRMRP implements a portfolio-driven approach by grouping related topic areas with strategic goals as a framework within which to address critical gaps in major research areas. All applications must address one of the FY26 PRMRP strategic goals as it relates to the portfolio-assigned FY26 PRMRP topic area. If the proposed research does not specifically address one FY26 PRMRP topic area and one FY26 PRMRP strategic goal, then the government reserves the right to administratively withdraw the application. The government reserves the right to reassign the application’s topic area if submitted to an incorrect topic area. The section below lists the FY26 PRMRP topic areas and strategic goals in each PRMRP portfolio category.

FY26 PRMRP Portfolio Categories with Associated FY26 PRMRP Topic Areas and FY26 PRMRP Strategic Goals

AUTOIMMUNE DISORDERS AND IMMUNOLOGY

All applications under this portfolio must be aligned to Autoimmune Disorders and

Immunology by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Celiac Disease

• Eczema

• Food Allergies

• Inflammatory Bowel Disease

• Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS)

• Sarcoidosis

• Scleroderma

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Investigate the mechanisms driving the pathobiology of the disease/condition.

• Investigate factors affecting disease/condition onset, progression, or heterogeneity, such as environmental exposures, comorbidities, behaviors, genetics, stress, infections, neuroimmune interactions, or microbiome dynamics.

• Investigate sex differences in the immune system.

Epidemiology

• Conduct patient-centered research to identify factors driving incidence trends, including recent increases.

• Conduct patient-centered studies to better understand differences between childhood- and adult-onset immune-mediated diseases/conditions, focusing on underlying pathobiology and treatment response.

• Conduct population-based studies to identify risk factors and enhance methods for detecting individuals at high risk.

• Conduct research to better understand sex differences in incidence and/or outcomes.

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• Conduct population-based studies to examine variations in incidence and outcomes across different population subgroups.

Prevention

• Develop and test innovative strategies to prevent the onset, relapse, and/or progression of the disease/condition.

• Identify and test approaches to establish immune tolerance early in life.

Diagnosis

• Identify and validate biomarkers for continuous monitoring of disease/condition progression or to evaluate intervention response.

• Develop and validate improved diagnostic tools to enable early, accurate detection and to standardize diagnostic strategies.

Treatment

• Develop and test curative and immune reset interventions.

• Develop and test therapies effective across all or multiple allergens or autoantigens.

• Develop and test strategies to improve outcomes, reduce inflammation, promote healing, provide neuroprotection, delay symptom onset, or minimize toxicity, including lifestyle changes, targeted drugs, nutraceuticals, and personalized treatments.

• Generate evidence for repurposing and off-label use of potential treatments.

CARDIOVASCULAR HEALTH

All applications under this portfolio must be aligned to Cardiovascular Health by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Brain Injury Impact on Cardiac Health • Hypoxia

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Investigate the mechanisms driving the pathobiology of the disease/condition.

• Investigate the mechanisms driving cardiovascular dysfunction following brain injury.

• Enhance understanding of oxygen sensing and the biological response to low oxygen levels.

• Identify risk factors, with a focus on comorbidities and genetic predispositions.

Epidemiology

• Conduct population-based studies to monitor cardiovascular changes over time.

• Conduct population-based research to identify risk factors, including but not limited to brain injury, and improve methods to detect individuals at high risk.

• Conduct population-based studies to examine variations in incidence and outcomes across different population subgroups.

Prevention

• Develop and test strategies to prevent or reduce the impact of the disease/condition on the heart, brain, arteries, and additional target organs.

• Develop and test strategies to reduce/prevent risk factors associated with disease onset, progression, or complications.

Diagnosis

• Develop and test strategies to enhance detection accuracy and sensitivity, including strategies to identify maladaptive vascular remodeling or to enable continuous monitoring or detection of tissue- or cell-specific oxygen levels.

• Develop and validate less invasive diagnostic methods.

• Identify and validate biomarkers that reliably predict outcomes.

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Treatment

• Generate evidence to support the repurposing and off-label use of treatments, including research on optimal dosing regimens.

• Develop and test innovative therapeutic strategies, with an emphasis on targeted, localized, and personalized approaches.

INFECTIOUS DISEASES

All applications under this portfolio must be aligned to Infectious Diseases by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Congenital Cytomegalovirus

• Hepatitis B

• Tuberculosis

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Investigate the mechanisms of infection, transmission, pathogenicity, or drug resistance.

• Develop innovative preclinical models to investigate disease pathobiology, host response, and to support drug discovery and testing.

• Enhance understanding of interactions between infection and comorbid conditions.

• Identify risk factors contributing to adverse outcomes.

• Discover and evaluate new drug targets.

Epidemiology

• Conduct population-based studies to collect data on disease trends, including those establishing, affiliated with, or contributing to clinical networks, biorepositories, or databanks.

• Conduct population-based studies to improve understanding of transmission, disease progression, and risk factors for complications.

• Conduct retrospective studies to assess the impacts of disease on quality of life.

Prevention

• Develop and test strategies to prevent complications and adverse outcomes following infection.

• Develop and test innovative strategies to prevent disease onset or inhibit its progression.

• Develop and test methods to eliminate maternal-fetal transmission.

Diagnosis

• Develop and validate innovative diagnostic tools, focusing on less- or non-invasive methods, point-of-care applications, early detection, or improved sensitivity.

• Identify and validate biomarkers to improve infection diagnosis and/or prognosis, assess infection-related complications, or measure protection against infection.

Treatment

• Develop and test curative interventions or treatments that eliminate all symptoms, including precision medicine approaches and those that address latent infection.

• Develop and assess new therapeutic strategies that are more potent, act directly, require shorter dosing regimens, provide longer-lasting effects, better mitigate complications, address treatment resistance, and/or address latent infection.

• Generate evidence for optimal treatment regimens, including strategies tailored to specific age groups, combination therapies, and antiviral or vaccine dosing schedule recommendations.

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INTERNAL MEDICINE

All applications under this portfolio must be aligned to Internal Medicine by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Accelerated Aging Processes Associated with Military Service

• Endometriosis

• Hypertrophic Dyschromia

• Infertility Associated with Military Aviators and Aviation Support Personnel

• Interstitial Cystitis

• Pancreatitis

• Polycystic Kidney Disease

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Improve understanding of how military service or exposures contribute to physiological dysregulation, reproductive health issues, the aging process, and epigenetic changes.

• Investigate the mechanisms and pathophysiology underlying disease onset and/or progression.

• Improve understanding of disease/condition heterogeneity, comorbidities, systemic impacts, and long-term complications.

Epidemiology

• Conduct comparative studies to determine military-specific risks and enhance understanding of diseases/conditions that have increased incidence in the active-duty and Veteran population.

• Conduct population- and/or patient-based studies to improve understanding of disease heterogeneity and phenotypic variability.

• Conduct research to better understand sex differences in incidence and/or outcomes.

• Conduct population-, occupational-, and/or patient-based studies to identify risk factors that influence disease development, progression, treatment, and outcomes.

Prevention

• Develop and test strategies to reduce the health impacts of military service and exposures and prevent long-term consequences.

• Develop and test innovative strategies to prevent disease onset, progression, and/or associated comorbidities.

Diagnosis

• Develop and validate screening tools to detect conditions associated with premature aging processes.

• Develop and validate innovative diagnostic approaches, focusing on less invasive methods, faster timelines, and methods that account for disease heterogeneity.

• Develop and validate biomarkers, imaging techniques, or other tools for diagnosis, objective prognosis, subtype differentiation, monitoring, or assessing treatment response.

• Develop and validate methods for identifying and measuring toxic agents and their pathophysiological effects.

Treatment

• Develop and test efficacy of lifestyle and other non-drug interventions.

• Develop and test novel treatment strategies aimed at cures or improved symptom management to enhance quality of life, including drug repurposing studies, combination therapies, and innovative drug delivery techniques.

• Develop and assess strategies to enable personalized care recommendations or optimize treatments for specific population subgroups, including studies on the efficacy of existing treatment options.

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• Develop and test innovative approaches for pain management as a symptom of the disease/condition.

• Develop and test innovative approaches to improve organ transplant outcomes or transplant alternatives, such as artificial organs, xenotransplants, and novel strategies to prevent rejection.

NEUROSCIENCE AND MENTAL HEALTH

All applications under this portfolio must be aligned to Neuroscience and Mental Health by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Brain Injury Impact on Cardiac Health

• Dystonia

• Eating Disorders

• Gambling Addiction

• Hydrocephalus

• Intranasal Ketamine Anesthetics

• Maternal Mental Health

• Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

• PANS and PANDAS

• Peripheral Neuropathy

• Post-Traumatic Stress Disorder

• Sleep Disorders and Restrictions

• Suicide Prevention

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Investigate the mechanisms underlying disease/condition pathobiology, progression, and associated comorbidities at multi-organ/system, circuit, or cellular/molecular levels.

• Identify factors that predispose individuals to the disease/condition, predict adverse outcomes, or contribute to resilience.

• Enhance understanding of disease/condition heterogeneity, including variations in phenotypic, symptom, and behavioral presentation.

• Develop and evaluate innovative models that can be used to understand etiology and will facilitate drug discovery and testing.

Epidemiology

• Conduct population-based studies to identify and track trends and treatment responses, generating data on treatment efficacy to inform the development of personalized treatments.

• Conduct population-based studies to enhance understanding of risk factors and progression of disease/condition.

• Conduct comparative studies to identify military-specific aspects of diseases/conditions, including risk factors, comorbidities, quality of life impacts, treatment preferences, prevalence, and ability to return to duty.

• Conduct research to better understand sex differences in incidence and/or outcomes.

• Conduct population-based studies to examine variations in incidence and outcomes across different population subgroups.

Prevention

• Develop and test strategies to prevent the disease/condition, as well as its downstream complications, including methods for relapse prevention or mitigation of risk factors.

• Develop and test innovative strategies to maintain optimal cognitive functioning and mental resilience.

Diagnosis

• Develop and validate objective diagnostic methods that are accurate, sensitive, enable early detection, and account for heterogeneity in disease/condition phenotypes, includes screening tools.

• Identify and validate biomarkers that predict risk for the primary disease/condition and its secondary complications.

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

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

FY26 Peer Reviewed Medical Clinical Trial Award 16

• Develop and validate methods for continuous monitoring and evaluating treatment efficacy.

Treatment

• Develop and test treatments to achieve curative or regenerative outcomes, preserve cognition, and enhance quality of life, including gene therapies, noninvasive stimulation techniques, alternatives to brain surgery, pharmaceuticals, and behavioral interventions.

• Evaluate repurposed drugs to accelerate strategies for improving symptom management and enhancing quality of life.

• Develop and assess guidelines for optimal intervention use, including evidence for safety and efficacy across diverse populations, precision medicine approaches, dosing regimens, safety monitoring, side effect management, and delivery methods.

• Develop and test innovative strategies to increase access to treatments, such as telemedicine approaches and adaptations tailored to specific populations.

ORTHOPAEDIC MEDICINE

All applications under this portfolio must be aligned to Orthopaedic Medicine by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Accelerated Aging Processes Associated with Military Service

• Musculoskeletal Health

• Orthotics and Prosthetics Outcomes

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Investigate mechanisms driving musculoskeletal disease/condition pathology and progression, focusing on muscle, connective tissue, genetics, epigenetics, aging, pain, sex differences, physical or mental stress, mechanobiology, cell senescence, and/or systemic interactions.

• Identify risk factors for orthopaedic diseases/conditions, including those that accelerate musculoskeletal degeneration, contribute to adverse outcomes, or lead to more severe symptoms.

• Develop and evaluate disease/injury using preclinical models to improve understanding of mechanisms and support intervention discovery and testing.

• Develop and evaluate small joint disease/injury models improve understanding of mechanisms and support intervention discovery and testing.

• Investigate the impact of life stage impacts musculoskeletal health and related diseases/ conditions, including the effects of childhood growth, hormonal changes throughout the lifespan, and aging-related processes.

Epidemiology

• Leverage large data sets to generate evidence-based treatment guidelines to optimize joint longevity.

• Conduct patient-reported outcomes research incorporating both objective measures and quality-of-life metrics to evaluate treatment efficacy and guide intervention decisions.

• Conduct research to better understand sex differences in incidence and/or outcomes.

• Conduct comparative studies to better understand musculoskeletal degeneration in

Veterans and identify military-specific risk factors.

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

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

FY26 Peer Reviewed Medical Clinical Trial Award 17

Prevention

• Develop and test strategies that improve point-of-injury care, focusing on reducing the risk of secondary complications and promoting joint preservation.

• Optimize and test personalized treatment or rehabilitation plans to address adverse outcomes and mitigate risk factors.

• Develop and test strategies to prevent inflammatory joint damage caused by aging or overuse.

Diagnosis

• Develop and validate strategies for early and precise diagnosis of musculoskeletal dysfunction, including screening methods tailored for pediatric populations.

• Identify and validate biomarkers that indicate the severity or progression rate of musculoskeletal disease or age-associated degeneration.

• Identify and validate biomarkers or outcome measures to monitor disease/condition progression, understand variability, assess treatment efficacy, and evaluate impacts on quality of life.

Treatment

• Advance innovative treatment strategies targeting etiology, preserving joint integrity, retaining functionality for daily activities, improving muscle strength and range of motion, reducing pain or fatigue, and/or regenerating damaged tissues.

• Develop and assess treatment strategies to enhance quality of life by increasing mobility, halting/slowing disease progression, or accelerating return to duty, including exercise regimens, regenerative or immune-modulating therapies, and device optimization.

• Develop and assess methods to optimize treatment, including patient-specific strategies, combination therapies, or refinement of intervention timing and dosing.

• Develop and test improved orthopedic devices, such as AI-driven auto-adjusting devices, better integrated designs for enhanced stability or accelerated healing, improved braces, prosthetic limbs, joint replacements, and strategies to enhance comfort.

RARE DISEASES AND CONDITIONS

All applications under this portfolio must be aligned to Rare Diseases and Conditions by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Angelman Syndrome

• Ehlers-Danlos Syndrome

• Facioscapulohumeral Muscular Dystrophy

• Fibrous Dysplasia/McCune-Albright Syndrome

• Fragile X

• Frontotemporal Degeneration

• Hereditary and Acquired Ataxias

• Hereditary Hemorrhagic Telangiectasia

• Hermansky-Pudlak Syndrome

• Mitochondrial Disease

• Myotonic Dystrophy

• Prader-Willi Syndrome

• Rett Syndrome

• Sickle-Cell Disease

• Spinal Muscular Atrophy

• von Hippel-Lindau Disease

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Develop and evaluate innovative models for drug discovery and testing, with an emphasis on patient-derived cell models.

• Investigate the mechanisms driving symptoms to identify new strategies for symptom management, including novel drug targets and paradigm-shifting insights into pathobiology.

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

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

FY26 Peer Reviewed Medical Clinical Trial Award 18

Epidemiology

• Conduct population- or patient-based studies to evaluate intervention efficacy, incorporating patient-reported outcomes and objective metrics to refine clinical guidance, develop personalized treatments, and validate clinically relevant endpoints.

• Conduct population-based studies to monitor disease progression and identify factors that drive onset, progression, and outcomes.

• Conduct population-based studies to improve understanding of relationships between the disease/condition and comorbidities or conditions with shared symptoms.

• Integrate electronic medical records with real world data to improve the accuracy of prevalence estimates and guide precision medicine approaches.

Prevention

• Develop and test approaches to prevent complications associated with the disease/ condition.

• Develop and test approaches, including gene therapy, to prevent symptoms or familial aggregation of the disease/condition.

• Develop and test evidence-based strategies to reduce disease/condition severity, including investigations promoting better health during pregnancy.

Diagnosis

• Develop and validate diagnostic strategies that are objective, noninvasive, accurate, and enable early detection, subtype distinction, disease progression tracking, and complication prediction.

• Develop and validate methods to objectively measure symptoms and evaluate their impact on daily functioning.

• Develop and validate diagnostic, monitoring, or prognostic biomarkers.

• Identify and validate clinically relevant endpoints for assessing treatment response, suitable for use in FDA-regulated clinical trials.

Treatment

• Develop and test innovative treatment approaches, emphasizing early intervention, therapies that slow/halt disease/condition progression, therapies that address phenotypic/ subtype differences, and disease-modifying or curative treatments.

• Develop and assess strategies to optimize existing treatments to reduce side effects and tailor interventions to specific patients.

• Generate evidence to support and guide the use of off-label drugs for symptom relief.

• Develop and test pharmacological or non-pharmacological interventions to manage symptoms and improve quality of life for patients and caregivers, including strategies for care transitions.

RESEARCH AND CLINICAL TOOLS

All applications under this portfolio must be aligned to Research and Clinical Tools by addressing one topic area and one strategic goal listed below.

TOPIC AREAS

• Proteomics

STRATEGIC GOALS BY CONTINUUM OF CARE

Foundational Studies

• Utilize proteomics to deepen understanding of the molecular mechanisms, progression, comorbidities, and long-term complications of the disease/condition/injury.

• Investigate the functional impact of post-translational modifications and proteoforms, beyond protein abundance, to guide management of the disease/condition/injury.

• Further the integration of proteomic…