NINDS Exploratory Clinical Trials for Small Business (R41/R44 Clinical Trial Required) is sponsored by National Institute of Neurological Disorders and Stroke (NINDS). This funding opportunity supports Small Business Concerns (SBCs) in submitting SBIR/STTR grant applications for investigator-initiated exploratory clinical trials. Projects must focus on products related to the mission and goals of NINDS, which includes epilepsy.

Expired PAR-24-044: NINDS Exploratory Clinical Trials for Small Business (R41/R42 Clinical Trial Required) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Neurological Disorders and Funding Opportunity Title NINDS Exploratory Clinical Trials for Small Business (R41/R42 Clinical Trial Required) R41 / R42 Small Business Technology Transfer (STTR) Grant - Phase I, Phase II, and Fast-Track Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 04, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 October 16, 2024 - Notice of Change: Update to Non-Responsive Criteria in PAR-23-311 and PAR-24-044.

See NOT-NS-25-002 . June 12, 2023 - Implementation of the NIH SBIR and STTR Foreign Disclosure Pre-award and Post-Award Requirements­­. See NOT-OD-23-139 .

February 23, 2023 - Notice of Change to Minimum Performance Standards for SBIR and STTR Applicants­­. See NOT-OD-23-092 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

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

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

Assistance Listing Number Notice of Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to provide a vehicle for Small Business Concerns (SBCs) submitting Small Business Innovation Research (SBIR) grant applications for investigator-initiated exploratory clinical trials to the National Institute of Neurological Disorders and Stroke (NINDS).

The projects must focus on products related to the mission and goals of the NINDS and may evaluate drugs, biologics, devices, or diagnostics, as well as surgical, behavioral or rehabilitation therapies. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to the application due date The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. New Date November 17, 2025 per issuance of NOT-OD-26-006 .

Required Application Instructions It is critical that applicants follow the SBIR/STTR (B) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description NINDS is committed to advancing diagnostics and treatments for people burdened by neurological diseases, and the NINDS Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs have provided the small business community with critical seed funding to support the development of a wide variety of technologies and therapeutics for the diagnosis and treatment of neurological diseases.

The SBIR/STTR Programs are structured in three phases. The main objective in SBIR/STTR Phase I is to establish the technical merit and feasibility of the proposed research and development (R&D) efforts, whereas in SBIR/STTR Phase II it is to continue the R&D efforts to advance the technology toward ultimate commercialization.

At the conclusion of an SBIR/STTR Phase II, it is expected that the small business concern (SBC) will fully commercialize their product or technology using non-SBIR/STTR funds in Phase III. The development of medical biotechnology products is often impeded by a significant funding gap (known as the “Valley of Death”).

In particular, the development of regulated products such as therapeutics and medical devices often requires several years and substantial capital investments, due in part to the high costs of clinical trials.

This NOFO supports applications from Small Business Concerns (SBCs) for exploratory clinical trials that contribute to the justification for a future trial to establish definitive efficacy (such as a Phase 3 clinical trial or a Pivotal device trial).

This includes Phase 1 and 2 studies of drugs and biologics, feasibility and preliminary efficacy studies of devices, as well as early studies of surgical, behavioral or rehabilitation therapies. This NOFO supports single-site and multi-site trials with up to three clinical sites.

Applications must aim to generate data that inform further clinical development of the proposed intervention or diagnostic, and in the case of FDA-regulated clinical trials applications must demonstrate readiness by including FDA approval of the proposed study. The earliest clinical studies should be designed to provide important initial information regarding the intervention (e.g., safety, tolerability, dosing) or diagnostic.

Midstage clinical studies will generally include randomization and blinding and should yield data that allow a clear go/no-go decision regarding whether the intervention should proceed to an efficacy trial. All applications must outline specific plans for future development in the event of promising results.

This NOFO is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy. Applications to implement definitive efficacy trials (e.g., Phase 3 clinical trials of drugs or Pivotal device trials) should be submitted to NINDS Efficacy Clinical Trials (UG3/UH3 ). See https://grants.

nih. gov/grants/guide/pa-files/PAR-21-237. html for more information.

This NOFO is not intended to support the conduct of clinical trials with more than three clinical sites. NINDS supports several clinical trial networks specifically designed to implement larger multi-site clinical trials. See https://www.

ninds. nih. gov/Current-Research/Research-Funded-NINDS/Clinical-Research for more information.

Renewal applications of SBIR Phase II awards (i.e., SBIR Phase IIB) to conduct Phase I and II clinical studies should be submitted to NINDS Renewal Awards of SBIR Phase II Grants (Phase IIB) for Clinical Trials and Clinical Research (R44).

The goal of this NOFO is to assist applicants in pursuing the next appropriate milestone(s) necessary to advance a product/technology that requires Federal regulatory approval or to bring a complex research tool to market.

To achieve this goal, the NOFO aims to facilitate the transition of clinical-stage projects to the commercialization stage by encouraging business relationships between NIH’s SBIR/STTR recipients and third-party investors and/or strategic partners. For this funding opportunity announcement Phase 1 and 2 clinical studies or trials refer to the common phases of a clinical trial.

SBIR Phase I and II refer to the project phases of the SBIR program. NIH defines a clinical trial as “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

” Scientific/Technical Scope Examples of appropriate studies under this NOFO include, but are not limited to, those designed to: Evaluate and optimize the dose, formulation, safety, tolerability or pharmacokinetics of an intervention in healthy volunteers or the target population.

Evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity, target engagement, dose-response trends, pharmacodynamic response) in a human "proof of concept" trial. Select or rank the best of two or more potential interventions or dosing regimens to be evaluated in a subsequent trial, based on tolerability, biological activity, or preliminary clinical efficacy (e.g., futility trials).

For devices: Establish proof-of-principle and optimize techniques, operation, and usability of a device; inform the final device design decisions; and estimate the magnitude of treatment effect.

Independent Third-Party Partners, As significant funding is often needed to take regulated clinical projects to market beyond initial clinical studies, we encourage applicants to develop business relationships between applicant SBCs and third-party investors/strategic partners who can provide substantial financing to help accelerate the commercialization of promising new products and technologies initiated with NIH SBIR or STTR funding.

Third-party partners include, but are not limited to, another company, a venture capital firm, an “angel” investor, a foundation, a university, a research institution, a state or local government, or any combination of the above.

In light of these goals, the NINDS strongly encourages applicants to establish business relationships with investors and/or strategic partners that have appropriate prior experience in the commercialization of emerging biomedical technologies.

That said, NINDS recognizes that companies developing products that have small potential revenue streams or that target small patient populations face additional barriers to market entry that make them less attractive to investors and strategic partners at preclinical or early clinical stages of development. Many of these technologies require complex clinical trial designs because of small and geographically diverse patient populations.

For the purposes of this NOFO, NINDS has defined small markets as development of novel products that: Address a rare disease, defined in the Rare Diseases Act of 2002 ( Public Law 107-280 ) as a condition affecting fewer than 200,000 individuals in the United States; or Qualify as a Humanitarian Use Device, defined as a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 persons in the United States per year; or Target a young pediatric population defined as including neonates (0-28 days), infants (<2 years), and/or children (2-12 years of age), as indicated in the FDA Premarket Assessment of Pediatric Medical Devices ; or Are complex research tools.

This is instrumentation comprising several distinct parts that must work together. Very often the goal of such projects is to deliver turnkey products for researchers.

For example, high density electroencephalography instrumentation includes electrode arrays, amplifiers, data analytic and data visualization software, etc. Another example is non-invasive near infrared imaging instrumentation, which might include photon sources and detectors, timing devices for delivering photons, amplifiers, and software. Some high throughput assay systems may fall into this category.

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

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

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

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

The proposed clinical trial must be based on a robust and rigorous scientific rationale (e.g., derived from non-clinical in vivo and/or in vitro studies or preliminary clinical studies) that demonstrates that there is an adequate scientific foundation to justify the proposed trial. The proposed trial design must also use rigorous and transparent approaches.

Applicants should take note of the following: (1) Consultation with NINDS: Applicants are encouraged to consult with NINDS Scientific/Research staff as plans for an application are being developed (see Section VII, Agency Contacts) and no later than 12 weeks prior to the anticipated application submission date.

This early contact will provide an opportunity to clarify NINDS policies and guidelines as well as to discuss how to develop an appropriate project timeline and milestone plan, which is subject to peer review. As well, discussions regarding strategies for recruitment and inclusion of women and minorities as participants in research involving human subjects are available.

(2) Other Relevant Programs: NINDS supports several clinical trial networks specifically designed to implement multi-site clinical trials. See https://www. ninds.

nih. gov/Current-Research/Research-Funded-NINDS/Clinical-Research for more information: NeuroNEXT ( http://www. neuronext.

org ): NINDS has a network called NeuroNEXT specifically designed to implement multicenter exploratory clinical trials (see https://www. neuronext. org/) and when appropriate, it is strongly preferred that such trials be performed within this network.

Therefore, applying to this exploratory clinical trials NOFO, an applicant should follow the instructions on the above website to obtain feedback on the suitability of their trial for NeuroNEXT. An important advantage of NeuroNEXT is that it can provide clinical, statistical and logistical expertise in developing study protocols as well as a standing national network of experienced clinical sites prepared to enroll study participants.

StrokeNet (http:// www. nihstrokenet. org ): NINDS has a network called StrokeNet specifically designed to implement multicenter exploratory and efficacy trials in stroke prevention, treatment and rehabilitation (see http://www .

nihstrokenet. org/). NINDS requires that all large stroke trials be considered for StrokeNet.

Only under exceptional circumstances will NINDS consider funding such trials outside of the StrokeNet program (see https://grants . nih. gov/grants/guide/notice-files/NOT-NS-14-043.

html). An important advantage of StrokeNet is that it can provide clinical, statistical and logistical expertise in developing study protocols as well as a standing national network of experienced clinical sites prepared to enroll study participants. EPPIC-Net ( https://www.

ninds. nih. gov/Current-Research/Trans-Agency-Activities/NINDS-Role-HEAL-Initiative/NINDS-Role-HEAL-Initiative-EPPIC ): The Early Phase Pain Investigation Clinical Network (EPPIC-Net) seeks to enhance the treatment of acute and chronic pain and reduce reliance on opioids by accelerating early-phase clinical trials of non-addictive treatments for pain.

EPPIC-Net has the capacity to quickly and efficiently conduct many simultaneous multisite studies. The network will conduct studies on a variety of treatments, including drugs and devices, as well as studies to better understand pain. Successful asset applicants do not receive funding but rather receive access to EPPIC-Net resources for conduct of the clinical trial for their asset.

Intellectual property and products studied within EPPIC-Net remain the property of the asset owner. SIREN ( https://siren. network/ ): NINDS supports the SIREN network which performs clinical trials that impact the care of the patient with a neurological emergency other than stroke in the pre-hospital or emergency department setting.

NINDS requires that all such trials be first considered for the SIREN network, though the study PI may come from outside of the network. The study PI will work with the SIREN network to write the protocol and lead the operations committee for the trial.

Before submitting an application to this NOFO, applicants should consult with NINDS scientific/research staff to obtain feedback on the suitability of their trial for one of these networks.

An important advantage of the networks is their capacity to provide clinical, statistical, and logistical expertise in developing study protocols, as well as a standing national network of experienced clinical sites prepared to enroll study participants. NINDS Cooperative Agreement (U44) Translational Programs.

NINDS has specific translational programs that utilize the SBIR cooperative agreement mechanism (U44), some of which allow preclinical and clinical trial activity within a single proposal. If eligible, companies are encouraged to apply through these programs. For more information visit: https://www.

ninds. nih. gov/Current-Research/Research-Funded-NINDS/Translational-Research .

(3) NIH Resources: As appropriate, applicants are encouraged to make use of the following resources for clinical research including: Clinical and Translational Science Award (CTSA) program ( https://ncats. nih. gov/ctsa ); NeuroQOL ( http://www.

neuroqol. org ); NIH Toolbox ( http://www. nihtoolbox.

org ); PROMIS ( http://www. nihpromis. org ); and NINDS Common Data Elements ( http://www.

commondataelements. ninds. nih.

gov ). Applicants are strongly encouraged to leverage existing NINDS research resources for their studies whenever possible. Such resources may include biospecimens from NINDS Human Biospecimen and Data Repository (BioSEND) or informatics system.

The NINDS BioSEND repository receives, processes, stores, and distributes biospecimen resources from NINDS funded studies that can be shared by the neuroscience research community, and currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva.

The NINDS Human Cell and Data Repository provides 1) disease-relevant stem cell lines for biomarker discovery, and/or 2) the capacity to bank blood for the creation of new cell lines relevant to their disease of interest. Leveraging the resources and support from neurological disorder advocacy groups, private research foundations, academic institutions, other government agencies and the NIH Intramural program are also encouraged.

Finally, applicants are encouraged to leverage the resources of ongoing clinical trials supported through other Federal or private funds. Applications proposing to collect biospecimens are strongly recommended to use the BioSEND protocols and procedures, and all specimens collected and banked with BioSEND must come from individuals who have consented to banking and sharing broadly with academia and industry.

Note that costs for collection are NOT included as a component of the NINDS Biomarkers Repository award. Therefore, most costs for the biospecimen banking are borne by the grantees utilizing this resource (see NOT-NS-15-046 ). Applicants planning projects in which biospecimens will be collected are strongly advised to consult the BioSEND website for more information about samples banked at the repository.

In addition, applicants are advised to consult with BioSEND staff to obtain a quote for biospecimen banking costs (email: [email protected] ). (4) IRB documentation: IRB approval is not required at the time of application submission, but is required prior to funding. As such, NINDS encourages investigators to begin these processes as early as possible.

NINDS also will require documentation of any other necessary regulatory approvals (e.g., Recombinant DNA Advisory Committee) prior to funding. Applicants are encouraged to review the NIH policy concerning single IRB for multisite clinical trials (see https://grants. nih.

gov/grants/guide/notice-files/NOT-OD-16-094. html and https://grants. nih.

gov/grants/guide/notice-files/NOT-OD-17-076. html ) as well as the sIRB requirement per the revised Common Rule at 45CFR46. 114 https://www.

hhs. gov/ohrp/regulations-and-policy/regulations/45-cfr-46/revised-common-rule-regulatory-text/index. html#46.

114 . (5) Study Rationale: The rationale for a clinical trial must be based on (i) an unmet medical need; (ii) a plausible biological mechanism; and (iii) robust supporting data, e.g., from non-clinical (in vivo and/or in vitro data) studies or preliminary clinical studies that demonstrate there is an adequate scientific foundation to justify the proposed trial.

The scientific premise for the trial should be based on preclinical and/or clinical data from rigorously performed studies (see http://grants. nih. gov/grants/guide/notice-files/NOT-OD-15-103.

html ). If previous research does not meet the rigor criteria outlined to an acceptable degree, applicants should address how the current study design addresses the deficiencies. (6) Efficacy: This NOFO is not intended to support the conduct of a clinical trial where the primary aim is to establish or confirm definitive efficacy (although under certain circumstances, early studies of preliminary efficacy can be a secondary aim).

While an exploratory clinical trial may examine clinical outcomes or biomarker outcomes as measures of "preliminary efficacy" as a secondary aim, it is important that it not appear to be an underpowered efficacy trial. Applications to implement definitive efficacy trials (e.g., Phase 3 trials of drugs or Pivotal device trials) should be submitted to PAR-21-237 , NINDS Efficacy Clinical Trials.

While an exploratory clinical trial may examine clinical outcomes or biomarker outcomes as measures of "preliminary efficacy" as a secondary aim, it is important that it not appear to be an underpowered efficacy trial.

(7) Effect Size: A drug or biologic trial will not be considered for funding under this NOFO when its primary objective is to estimate intervention effect size to be used in power calculations for a future efficacy clinical trial. Effect size estimates based on small or short-term studies are often unreliable.

Power for an efficacy trial should be based on the smallest clinically meaningful effect size, which is often determined by surveying physicians or patients, or by comparison to the effect produced by existing interventions .

(8) Ancillary studies: Ancillary studies, defined as research undertaken to address scientific questions relevant to the parent study and that require access to data or records from the parent study, and/or involve collection of additional data, specimens, or records, are not permitted within the clinical trial application.

Applicants are advised to discuss their ideas with Scientific/Research staff for direction on an appropriate funding mechanism. (9) Secondary Aims: For drugs and biologics, issues of study feasibility and refinement of study procedures may be addressed as secondary aims in a clinical trial, but not as the primary aim.

Examples of such secondary aims include Determining the optimal measure (endpoint), its variability, and/or the optimal timing of outcome evaluations in the context of the intervention Collecting information on the utility of questionnaires, rating scales, or biomarkers Developing and refining data collection procedures. Optimizing the administration of the study intervention.

Developing and refining standardized methods of assessing outcome. Optimizing methods for identifying, recruiting, and retaining study participants. For Early Feasibility or Traditional Feasibility studies of medical devices, issues of study feasibility and refinement of study procedures are expected to be addressed as primary aims in addition to providing initial clinical safety data at this stage.

These may include: Identifying appropriate modifications to the procedure or device to enable a subsequent Pivotal study on a finalized system; Refining the intended use population; Developing and refining data collection procedures; Refining the non-clinical test plans or methodologies; and Developing subsequent clinical study protocols.

(10) Multiple Trials: There may be several questions to be answered before a phase 3 efficacy trial can be designed and conducted. The proposed study is not required to address all potential questions, but the applicant should clearly detail the overall clinical development plan for the intervention, which could involve more than one exploratory trial.

(11) Innovative Designs: The use of innovative and efficient study designs is encouraged, such as adaptive dose-finding designs, designs incorporating plans for sample size recalculation, preliminary efficacy for devices, and futility designs.

Applications for Phase 1 trials in the patient population are encouraged when appropriate (e.g., certain rare diseases), as are applications that encompass Phase 1 and Phase 2 studies (early proof of mechanism or proof of concept). Applications Phase 3 trials should be submitted under PAR-21-237 , NINDS Efficacy Clinical Trials.

For medical devices, Traditional Feasibility study designs may include, for example, single-arm studies, on-off interventions (patients as their own controls), device-device comparisons, device-drug comparisons, comparisons to historical controls, comparisons to performance criteria/goals, adaptive designs, and Bayesian designs.

(12) Pharmacometrics: Applications seeking to obtain data needed for pharmacometric modeling are encouraged, with the aim of enabling the optimal design of a future efficacy trial of an intervention.

(13) Innovative Technologies: Applicants are encouraged to consider utilizing (at least experimentally) digital/mobile/sensor technologies and web-based systems to facilitate data collection (including data collection in a continual, contextual, real-world setting rather than through a traditional milestone-based approach), as well as to enhance protocol adherence.

(14) Rare Diseases: Trials in rare diseases are encouraged, particularly in conditions for which definitive outcome measures and prior data from natural history studies are available.

It is recognized that available patient pools may not be adequate to meet the sample size requirements typically seen in trials in more common disorders of the nervous system, and innovative trial designs, including crossover designs and adaptive designs, can be appropriately considered.

Additionally, an assessment of clinical efficacy as a secondary outcome may be warranted for rare diseases where the available patient pool may not make a definitive efficacy trial feasible. Regardless of the design it is especially important to ensure that the study design and statistical analysis plans will meet the stated objectives, and allow for the most efficient evaluation of the limited subjects.

The application should clearly demonstrate recruitment feasibility at the participating site and applicants are encouraged to fully engage patient advocacy groups or similar representatives of the affected disease community in study design, execution, and reporting.

(15) Relationships with Patient Groups: Applicants are strongly encouraged to establish relationships with patient groups and solicit their input on recruitment, the clinical meaningfulness of the question under study, the relevance of the proposed clinical outcomes, and approaches to minimizing the burden on study subjects (16) Biomarkers: Applications are encouraged that evaluate preliminary efficacy based on early signals of activity on biomarkers or clinical endpoints, or that mechanistically test the activity of an intervention in terms of its presumed target(s).

However, this NOFO is not appropriate for applications primarily intended to discover biomarkers. Applications Not-Responsive to this NOFO: Non-responsive applications will not be reviewed. Applications for Phase 3 trials.

These projects should be submitted under PAR-21-237 , NINDS Efficacy Clinical Trials. Applications for a clinical trial where the primary aim is to establish or confirm definitive efficacy. Applications to implement definitive efficacy trials (e.g., Phase 3 trials of drugs or Pivotal device trials) should be submitted to PAR-21-237 , NINDS Efficacy Clinical Trials.

Trials where the primary objective is to estimate intervention effect size to be used in power calculations for a future efficacy clinical trial. Multi-site clinical trials with more than three clinical sites. These trials may be supported through NINDS clinical trial networks, such as StrokeNet ( http://www.

nihstrokenet. org ), NeuroNEXT ( http://www. neuronext.

org ) and EPPIC-Net ( https://www. ninds. nih.

gov/Current-Research/Trans-Agency-Activities/NINDS-Role-HEAL-Initiative/NINDS-Role-HEAL-Initiative-EPPIC ). Preclinical activities to support filing of an IND or IDE followed by clinical trial activities supported by this IND/IDE.

Studies requiring an IND/IDE where the applicant has not demonstrated that their intervention falls into one of the following scenarios: (a) The protocol has been submitted under an open IND and the IND is not under full or partial hold. Under this scenario, applicants must provide documentation such as a "may proceed" email or letter from the FDA.

(b) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has fully approved the IDE or IDE supplement. Under this scenario, applicants must provide documentation of an IDE or IDE supplement full approval letter from the FDA. (c) The protocol has been submitted under an IND and is on full or partial hold.

Under this scenario applicants must provide full documentation from the FDA on the reasons for hold and the FDA recommendations. Applicants should discuss how they intend to address the hold issues and when they believe they will have FDA approval to proceed with trial implementation. (d) The protocol has been submitted as an original IDE or as a new study under an open IDE, and FDA has conditionally approved the IDE or IDE supplement.

Under this scenario applicants must provide full documentation from the FDA on the conditions of approval. Applicants should discuss how they intend to address these conditions and when they believe they will have FDA approval to proceed with trial implementation. (e) The protocol is exempt from an IND.

Under this scenario applicants must provide a copy of the exemption letter from the FDA. (f) The protocol is either exempt from the IDE regulations or does not require IDE approval because it is determined to be nonsignificant risk. Under this scenario applicants must provide either an IDE exemption letter or a copy of the risk determination letter from the FDA.

For devices, if the IRB has determined that the device is Non-Significant Risk, documentation from the IRB is acceptable. (g) The study is of a non-regulated intervention, including surgical and behavioral interventions. Provide a Non-Significant Risk documentation of your intervention from an IRB.

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

Section II. Award Information Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed New (Phase I, Fast-Track) Resubmission (All Phases) The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Only those application types listed here are allowed for the NOFO. Required: Only accepting applications that propose clinical trial(s) Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Total funding support (direct costs, indirect costs, fee) normally may not exceed $295,924 for Phase I awards and $1,972,828 for Phase II awards. NIH has received a waiver from SBA, as authorized by statute, to exceed these total award amount hard caps for specific topics. The current list of approved topics can be found at https://sbir.

nih. gov/funding . Applications should not exceed $700,000 in total cost for Phase I, with no more than $500,000 total costs in any year, and $3,000,000 total costs for Phase II with no more $1,500,000 in total cost in any year.

Applicants are strongly encouraged to contact program officials prior to submitting any application in excess of the hard caps listed above and early in the application planning process. In all cases, applicants should propose a budget that is reasonable and appropriate for completion of the research project. Durations up to 2 years for Phase I and up to 3 years for Phase II may be requested.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III. Eligibility Information Only United States small business concerns (SBCs) are eligible to submit applications for this opportunity.

A small business concern is one that, at the time of award of Phase I and Phase II, meets all of the following criteria: Is organized for profit, with a place of business located in the United States, which operates primarily within the United States or which makes a significant contribution to the United