RFA-DC-25-005: In Vivo High-Resolution Imaging for Inner Ear Visualization (R01, Clinical Trial Optional)

RFA-DC-25-005: In Vivo High-Resolution Imaging for Inner Ear Visualization (R01, Clinical Trial Optional)

This NIH R01 Notice of Funding Opportunity (NOFO) supports development of in vivo, high-resolution structural and functional imaging for the living human inner ear. It is administered by the National Institute on Deafness and Other Communication Disorders (NIDCD), a component of the National Institutes of Health. The notice is aimed at technology that can show auditory and vestibular structures in awake humans with substantially greater detail or accuracy than current methods provide.

The current listed submission date is October 1, 2026, at 5:00 PM local time of the applicant organization. The earlier June 3, 2026 date has passed, but the October receipt date remains in the official key-date table. NIH states that no late applications will be accepted. The notice expires on October 2, 2026, so applicants need to work from the October receipt date rather than treating the page as an open-ended or rolling program.

Key details at a glance

What this opportunity funds and what it explicitly does not fund

This NOFO is a targeted imaging opportunity, not a general funding stream for auditory health work. The supported work should address structural or functional imaging of the human inner ear and should explain how the proposed method can reach human use. Responsive projects can include:

• Development of new non-invasive in vivo techniques with materially improved spatial, temporal, or functional resolution in humans.
• Improvement of existing methods (hardware/software/protocol-level upgrades) to increase signal quality, contrast, and diagnostic power.
• Development of imaging probes and contrast agents to visualize inner-ear structures.
• Translation-focused work that moves an imaging method toward non-invasive use with awake humans in a clinical setting.

The notice also allows studies in humans and intermediate studies in mammalian animal models. An animal or anesthetized-human study must explain its path toward awake-human application, or clearly state its limitations and usefulness. A multidisciplinary team is encouraged when the project needs complementary imaging, engineering, biological, and clinical expertise.

The program explicitly emphasizes structure and function where prior methods are insufficient and where imaging can materially improve diagnosis and care pathways for hearing, balance, and related communication disorders.

It is not meant for a broad diagnostic platform with no credible inner-ear application. The NOFO says that the following are not responsive:

• Proposals without realistic translation to imaging inner ear structures in humans.
• Non-mammalian work disconnected from human relevance.
• High-risk clinical trials.
• Applications proposing more than one clinical trial in a single submission.
• Applications that omit the required five-point Research Strategy structure.

The five required points are substantive application instructions, not optional suggestions:

1. Specify what imaging dimension is improved (spatial, temporal, or functional).
2. Quantify likely resolution increase and explain clinical impact.
3. Give a timeline and detailed plan for taking the work into a clinical setting for non-invasive use with awake humans. If the method can only be used invasively, in anesthetized humans, or in animals, explain its limits and possible translation solutions.
4. Describe the clinical settings and conditions in which the technique could be used, how it would inform care and management, and how it could guide clinical decisions.
5. Describe the auditory or vestibular pathologies that could be better diagnosed and any treatments that could be informed by the improved imaging.

If your idea does not clearly satisfy these, the application is likely to fail before scoring.

Clinical-trial boundary and relationship to the companion U01

The companion opportunity is the U01 (RFA-DC-25-003) for high-risk clinical trials. RFA-DC-25-005 may include one NIH-defined clinical trial, or no trial, but a proposed trial must satisfy every condition in the notice. It must be low risk to participants, not require FDA oversight such as an IND or IDE, not be an NIH-defined Phase III trial, and be intended to gather scientific evidence for later studies rather than directly change health policy or the standard of care.

From the NOFO language, this distinction is operational, not just semantic:

• Allowed: a low-risk human imaging trial that is hypothesis-driven and produces data needed for later scientific, design, implementation, or clinical work.
• Allowed: a non-trial imaging project involving humans or mammalian intermediate studies when the research is relevant to the NIDCD mission and has a credible human-use path.
• Excluded: a trial needing IND or IDE oversight, a high-risk trial, a Phase III efficacy study, or an application containing more than one clinical trial.

In practice, if your proposal needs regulatory-heavy risk management, adverse event complexity, or direct treatment claims, it likely belongs in a different NOFO, and you should use this one only if the technical objective remains fundamental imaging development.

Who is eligible and who should treat this as high-risk for scope

Eligibility is broad by NIH standards. The NOFO lists the following eligible organization categories:

• public and private institutions of higher education,
• nonprofits (including 501(c)(3) and non-501(c)(3)),
• for-profits including small businesses,
• local government entities,
• federal government entities,
• tribal and regional organizations in eligible categories,
• independent school districts, public housing authorities, Native American tribal organizations, faith- or community-based organizations, regional organizations, and foreign organizations.

Foreign organizations and foreign components of U.S. organizations are eligible under this NOFO. The notice also states that NIH will not issue awards involving foreign subawards or subcontracts unless the NOFO is specifically designated for funded international collaborations. That distinction matters for a proposal whose international work would require a funded subaward.

The applicant organization must complete and maintain the required registrations before submission. The notice warns that registration can take six weeks or more, and that an incomplete registration is not a valid reason for a late application. The main gates are:

1. Organization registration: maintain active System for Award Management (SAM) registration and complete Grants.gov registration. The organization must also have the required unique entity information and eRA Commons affiliation.
2. PI and role setup: every PD/PI needs an eRA Commons account, and the PD/PI profile must be linked to a valid ORCID ID. If one person serves as both PD/PI and Signing Official, NIH requires distinct eRA Commons accounts for those roles.
3. Clinical-trial classification: decide early whether participants are prospectively assigned to an intervention. If the answer is yes, the application must include the required human-subjects and clinical-trial information.
4. One-trial limit: include no more than one clinical trial, and verify every low-risk condition before the application is submitted.

The NOFO itself is explicit that applications with registration gaps are at risk of late submission and do not receive waiver discretion.

Funds, budget logic, and the direct-cost limit

The official award section gives a program-level planning figure and a per-grant budget rule:

• NIDCD intends to commit $3M in FY 2025 for 4–6 awards combined across this NOFO and the companion RFA-DC-25-003.
• Future-year amounts depend on annual appropriations, with $2M planned in both FY 2026 and FY 2027.
• Maximum funding per grant must be less than $500,000 in direct costs per year unless NIDCD prior approval is obtained.

In practical terms, treat this as a program where fit and technical execution matter more than scale.

Because the direct-cost rule is explicit:

• the budget should reflect the actual needs of the proposed project;
• a request at or above the threshold requires advance contact and prior approval from NIDCD; and
• the period of support should follow the scope of the project, up to a maximum of five years.

The project period is not fixed; it is determined by scope up to a maximum of 5 years. That can be useful for teams proposing a phased imaging roadmap, but still requires a realistic staffing and facility plan that maps to publication and validation windows.

Application timeline and process for 2026/2027 planning

The official table contains four receipt dates for the reissued notice:

• June 3, 2025, followed by November 2025 scientific merit review, January 2026 advisory council review, and March 2026 earliest start.
• October 1, 2025, followed by March 2026 scientific merit review, May 2026 advisory council review, and July 2026 earliest start.
• June 3, 2026, followed by November 2026 scientific merit review, January 2027 advisory council review, and March 2027 earliest start.
• October 1, 2026, followed by March 2027 scientific merit review, May 2027 advisory council review, and July 2027 earliest start.

The October 1, 2026 row is the next available listed receipt date. The October 2, 2026 expiration date follows it, so a team should not assume that an application can be submitted after the October receipt date.

Review and award cycles in the NOFO key-date table pair each full submission set with likely peer review, council review, and earliest start windows through 2027.

Suggested planning sequence (practical)

For the remaining listed cycle, teams should plan backward from October 1, 2026:

• First: define whether the project is a clinical trial and whether it fits the low-risk criteria. Contact NIDCD staff early if the classification, scope, or budget threshold is uncertain.
• Next: set measurable imaging targets, identify the clinical setting, and build the five-point Research Strategy around the path to awake-human use.
• Before drafting: make sure SAM, Grants.gov, eRA Commons, unique-entity, ORCID, and any applicable foreign-organization registrations are complete. Do not wait for the receipt date.
• During assembly: prepare the SF424 (R&R) components, Research Plan, human-subjects or clinical-trial records when applicable, Data Management and Sharing Plan, and other required resource-sharing materials.
• Before submission: check page limits, application-type restrictions, budget justification, and the organization’s submission authority. Submit early enough to view the application in eRA Commons and correct errors before the deadline.

NIH explicitly expects early submission to reduce late-stage submission errors.

Submission systems and route

This NOFO accepts three electronic routes:

• NIH ASSIST.
• An institutional system-to-system solution.
• Grants.gov Workspace.

The application package must be accessed through one of those routes. After the Grants.gov submission, the applicant must track the application in eRA Commons, view it before the due date, and correct any errors in time. The notice says that applications that do not conform to the NOFO and the NIH How to Apply instructions may be delayed or not accepted for review.

Required materials and what the reviewers will look for

The NOFO does not reward generic imaging proposals. It rewards proposals that prove translation feasibility.

Required core sections

• Standard NIH SF424(R&R) forms and profile sections.
• Full response to the five required points in the PHS 398 Research Plan’s Research Strategy.
• A specific plan for clinical translation and the conditions of use in awake humans, or a justified explanation of limitations if the work cannot yet reach that setting.
• A Data Management and Sharing Plan when the research will generate scientific data.
• Resource-sharing plans as required by the NIH Application Guide.
• Human-subjects and clinical-trial records when the project involves those activities.
• Vertebrate-animal, biohazard, inclusion, and other attachments when applicable.

Clinical trial posture (if included)

If your application includes a human trial component, make sure all NIH criteria are explicitly satisfied:

• No FDA oversight such as an IND or IDE is required.
• The intervention is low risk to participants.
• The trial is not an NIH-defined Phase III study intended to establish efficacy.
• The study gathers evidence to inform later work rather than directly changing health policy or the standard of care.
• At most one clinical trial appears in the application.

Any proposal that sounds like efficacy proof in this pathway should not proceed under this NOFO.

Compliance and policy anchors

Beyond NIH science review, successful submission requires attention to:

• SAM.gov validity and UEI alignment.
• eRA Commons role setup for PD/PI and signing official.
• Institution-level submission authority alignment.
• Data and safety requirements for clinical work.
• ClinicalTrials.gov registration posture for applicable trials.

Skipping these does not usually disqualify by science but can fail intake and delay review.

Review criteria and how to strengthen a submission

NIH evaluates applications through scientific and technical peer review, followed by a second-level review by the appropriate Advisory Council or Board. For this NOFO, the application should make four things easy for reviewers to judge:

• Specificity of imaging gain: state whether the improvement is spatial, temporal, functional, or a combination, and quantify the expected change against current techniques.
• Feasible translational bridge: define where in the clinic this improves decisions.
• Team sufficiency: combine technical and clinical expertise.
• Scope control: avoid trying to do full productization, diagnostics, and broad commercial translation in a single grant year.

Section V applies NIH’s review factors and topic-specific checks:

• Innovation is not enough alone; impact requires a clinical pathway.
• Rigor in study design, safety handling, and reproducibility.
• If human subjects are included, review considers risk control, inclusion, protections, and data validity.
• For vertebrate work, methodologic and welfare standards are weighted.

Reviewer traps to avoid

• Submitting a high-risk intervention plan under the low-risk NOFO.
• Confusing this NOFO with the companion U01 clinical trial arm.
• Omitting one of the five required Research Strategy points.
• Underestimating time needed for registrations and account setup.
• Over-promising translational outcomes without a realistic clinical workflow.

Projects that stay disciplined on technical novelty and clinical value, and that explain how data will drive diagnosis or treatment planning, usually resonate better than broader “imaging tool” proposals.

Common mistakes and pre-submission checklist

Use this checklist before finalizing:

• Confirm the October 1, 2026 receipt date and the 5:00 PM local-time cutoff.
• Confirm one of the two paths: non-trial project or low-risk clinical trial.
• Confirm only one clinical trial is included.
• Check that the project directly targets human inner ear resolution (not generic imaging).
• Complete NIH registration requirements early (SAM, UEI, eRA Commons, Grants.gov).
• Include all required plans: data management, resource sharing, safety, human subjects (if relevant).
• Keep the grant below $500,000 in direct costs per year unless NIDCD prior approval is secured.
• Build and maintain explicit milestones linked to proposed grant-year spending.
• Provide translation pathways and diagnostic context early in the narrative.

If your team must decide between this RFA and RFA-DC-25-003, ask whether the proposed trial can proceed without high-risk exposure, FDA oversight, or a Phase III efficacy objective. If not, the companion U01 is the relevant notice to examine.

Frequently Asked Questions

Is this still useful for 2026/2027 planning now?

Yes. The official table lists an October 1, 2026 receipt date with scientific merit review in March 2027, advisory council review in May 2027, and an earliest start date in July 2027. The notice expires on October 2, 2026.

Is this only for basic science with no human work?

No. It supports both non-trial and low-risk NIH-defined clinical trial projects, provided the trial remains low-risk and limited as required by the NOFO.

Can foreign groups apply?

Yes. Foreign organizations and foreign components of U.S. organizations are listed as eligible, but applicants must satisfy NIH registration and application requirements. The notice separately limits foreign subawards and subcontracts unless the NOFO is designated for funded international collaborations.

Is this a one-year award?

No. Project period is determined by scope and can be up to 5 years.

Do I need a resource-sharing plan?

Yes. Resource sharing and data-management requirements apply broadly under NIH policy and were reinforced for this opportunity.

Is the funding guaranteed at $2M per year?

No. The $2M figures for FY 2026 and FY 2027 are planned amounts, and the notice says future-year funding depends on annual appropriations. The per-grant budget still must reflect the project’s actual needs and stay below the direct-cost limit unless NIDCD approves otherwise.

Official links and monitoring

Official opportunity page: https://grants.nih.gov/grants/guide/rfa-files/RFA-DC-25-005.html

Related companion opportunity (higher-risk clinical trial path): https://grants.nih.gov/grants/guide/rfa-files/RFA-DC-25-003.html

NIH application guidance references are in the same source, including submission contacts and instructions pages in the NOFO.

Because this NOFO has multi-round structure and changing NIH guidance, monitor the page for updates before finalizing your submission plan.