The Common Fund Venture Program is a new area of Common Fund support that provides a framework for development of short-term Common Fund initiatives that embrace bold approaches and are responsive to the shared priorities of NIH Institutes, Centers, and the Office of the Director.

Venture initiatives are Common Fund investments and so must meet Common Fund criteria, as expressed below. However, additional criteria also apply, emphasizing brief, modest investments that can be implemented quickly in response to emerging opportunities. Venture investments should be lightweight and nimble while having a strong potential to accelerate science quickly.

What makes Venture initiatives special?

• They are Bold: they are daring investments with potential for significant, outsized impact
• They are Nimble: they can be implemented rapidly in response to scientific opportunity
• They are Focused: they are limited to three years, up to $5 million annually to invest in a clearly defined research topic

What makes Venture initiatives consistent with the Common Fund?

• Common Fund criteria will apply to Venture investments, with accelerated timelines and nimble project management. Venture initiatives will be:
  • Transformative: projects have strong potential for exceptionally high and broadly applicable impact in biomedical/behavioral research
  • Catalytic: projects are time-limited investments of 10 years or less, designed to capitalize on new scientific knowledge or breakthroughs to accelerate and enable subsequent research
  • Goal-driven: projects include defined goals to develop specific deliverables (such as new knowledge, data sets, resources, methods, or technologies)
  • Synergistic: projects advance the missions of multiple ICOs, and are relevant to multiple diseases or conditions
  • Novel: projects pursue innovative solutions to specific scientific challenges important to the NIH mission but that no other entity is likely or able to address
• Venture initiatives are not:
  • Pilot programs to prepare for larger Common Fund investments
  • A means to address high-priority projects for individual ICOs
  • Support for exploratory, open-ended research without specific goals and milestones
• Governance:
  • Ideas for new Venture initiatives are submitted through the ICO Directors to the Office of Strategic Coordination, which oversees the NIH Common Fund, leveraging public input as appropriate. Initiative idea submissions can derive from any areas of biomedical and behavioral research. All proposals are evaluated for responsiveness to the Common Fund and Venture criteria, and are considered by the Venture Board, made up of ICO Directors. Promising ideas are recommended by the Board for full development. The NIH Director provides final approval. Updates on the progress of each Venture initiative will be described on their individual website. 

What is the Venture Advancing Non-Invasive Optical Imaging Approaches for Biological Systems (NIOI) Initiative? 

The Common Fund Advancing Non-Invasive Optical Imaging Approaches for Biological Systems (NIOI) Venture Initiative aims to develop next-generation non-invasive or minimally invasive optical imaging techniques to overcome the problem of light scattering in biological systems. Enhanced imaging techniques can make possible earlier detection of conditions, more precise evaluation of cellular and tissue health, and advancements in non-invasive or minimally invasive procedures, ultimately improving patient outcomes and reducing the need for more invasive methods. 

What is the title of this Notice of Funding Opportunity (NOFO)?

In Vivo Non-Invasive Optical Imaging Approaches for Biological Systems (UG3/UH3 Clinicals Trial Not Allowed)

What is the Announcement Number of this NOFO?

RFA-RM-24-012

What is the purpose of this announcement?

The purpose of this announcement is to invite applications from eligible organizations to support the development of next-generation non-invasive or minimally invasive optical imaging techniques to overcome light scattering limitations, resulting in high spatial and temporal resolution optical images at significantly greater depths within biological tissues than is currently possible.

Whom can I reach out to with questions about this announcement?

All questions are welcome. Please reach out to Jonathan D. Pollock, Ph.D. ([email protected]). Please also reach out to Pam Fleming ([email protected]) with any financial/grants management questions.

What organizations are eligible?

• Higher Education Institutions
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
• The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
• Nonprofits Other Than Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
• Federal Government
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Will foreign institutions be eligible?

• Non-domestic (non-U.S.) Entities (Foreign applicants) are not eligible to apply.
• Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
• Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Can an NIH Intramural Research Program (IRP) investigator submit an application for the NIOI initiative?  

No. IRP investigators cannot apply as the prime recipient for the NIOI initiative.  

Can NIH IRP investigators participate as collaborators with the lead recipient for the NIOI initiative? 

• Yes. NIH IRP investigators can participate in the Venture Program NIOI initiative, with certain limitations. Intramural investigators may collaborate with extramural investigators when both have expertise that could contribute to the goals of the program.  
• For projects that involve IRP investigators, separate letters originating from and signed by each participating IRP investigator’s Scientific Director must be included in the application, in accordance with the NIH Intramural Sourcebook. The letter(s) must describe the intramural aim(s) and include the requested budget and justification for the intramural activity. 
• The number of person months and justification for all federal employees who will be committed to the project must be included in the letter, in accordance with the NIH Intramural Sourcebook. This will allow the reviewers to evaluate the suitability of proposed staff to conduct the work.

Can NIH IRP investigators request salary funds for their effort in the project?

No. No support may be requested from any federal agencies, including the NIH intramural program, for salary or related fringe benefits for career, career conditional or other federal employees (civilian or uniformed series) with permanent appointments under existing position ceilings or any costs related to administration of facilities support.

Can NIH IRP investigators request funds for the project other than their salary? 

• Funds may be requested for IRP investigator participation and are limited to the costs required for carrying out the proposed work, provided those costs can be specifically identified with the Venture Program NIOI initiative. 
• Costs may include:
  • Salary for staff to be specifically hired under a temporary appointment for the project
  • Consultant costs
  • Equipment
  • Supplies 
  • Travel
  • Other items typically listed under Other Expenses.

Where in the application should IRP investigators include a budget request and justification?

IRP investigator costs must not be included in the application budget request or budget justification to RFA-RM-24-012.  Instead, a specific IRP budget request must be included in the letter(s) from the Scientific Director(s).  

In which sections of the application should include IRP investigator participation be described? 

Include IRP investigator participation in the Research Strategy, Leadership Plan, Milestone and Deliverables, Biosketches, Plan for Enhancing Diverse Perspectives, and PHS Human Subjects and Clinical Trials Information.  Information (if relevant) for all other sections (Equipment and Facilities, Institutional Letter of Support, Budget and Budget Justification, Resource Sharing Plan, Data Management and Sharing Plan) should be provided in the Letter from the IRP investigator’s Scientific Director.

How are funds requested for the IRP investigator and/or related to IRP participation provided if the project is selected for funding? 

The project budget, including for the IRP investigator and/or IRP participation, will be determined prior to award.  For projects selected for funding, IRP investigator funds will be issued through an Interagency Agreement (IAA) and terms and conditions of funding included in an associated Memo of Understanding (MOU).

Can other federal agencies of the US Government apply to the NIOI initiative through Research Opportunity Announcement RFA-RM-24-012? 

Yes, other federal agencies of the US Government may apply to the NIOI initiative EXCEPT for NIH investigators, who cannot apply as the prime recipient.  See FAQs for participation of Intramural Research Program investigators as collaborators. 

Can I apply for this opportunity without submitting a Letter of Intent (LOI)?

Yes. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review.

What is a PEDP?

A PEDP or “Plan for Enhancing Diverse Perspectives” is a summary of strategies to advance the scientific and technical merit of the proposed project through inclusivity. This plan should be applied throughout all of the proposed NIOI research plans.

What does "diverse perspectives" mean for a research project?

Broadly, diverse perspectives refer to the people WHO* do the research and the places WHERE** research is done, as well as WHO PARTICIPATES*** in the research as part of the study population.

• *WHO: The inclusion and empowerment of investigators and trainees from a variety of backgrounds, including those traditionally underrepresented in the biomedical research workforce (see NOT-OD-20-031), and investigators from different scientific disciplines, at varying career stages, and with varied skills, experience, and expertise.
• **WHERE: Participation of researchers from all relevant sectors, including diverse organizations and institutions (e.g.  research intensive and research-active, undergraduate, minority-serving, community-based etc.). Historically, largely well-resourced academic and research institutions have competed successfully for NIH funding. The goal is to broaden the NIOI initiative’s reach by supporting projects, partnerships, and collaborations at institutions and organizations that, to date, have not often been part of NIH-funded work.
•  ***WHO PARTICIPATES: To realize the broadest benefits to human health impacting all segments of the population, the NIOI initiative is committed to promoting equity in research participation. To that end, maximum effort is encouraged to engage and recruit diverse participants for human studies. To make findings broadly relevant, it is expected that projects involving human participants or samples derived from humans should be collected in an ethically sound manner and consented appropriately.

How do PEDPs vary?

The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. Where possible, applicant(s) should align their description with the required elements within the research strategy section. The PEDP should include a timeline and milestones for relevant components. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations  (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).

What must the PEDP include?

• Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project.
• Anticipated timeline of proposed PEDP activities. 
• Description of how the PEDP will advance the scientific and technical merit of the proposed project.
• Evaluation methods for assessing the progress and success of PEDP activities Anticipated timeline of proposed PEDP activities.

What guidance on the PEDP is available for applicants?

Please see NIH PEDP Guidance materials. Questions not covered in the NIOI FAQs and the NOFO can be directed to [email protected]. Additional guidance and FAQs will be updated as needed.
 

What is the budget for this opportunity?

The Common Fund Venture Initiative may allocate up to $4,900,000 total (direct + F&A) costs per year for all awards. Support of 3 or 4 projects is anticipated. 

The funding decisions will consider (1) the scientific and technical merit of the proposed project, including the PEDP, as determined by scientific peer review, (2) availability of funds and (3) relevance of the proposed project to programmatic priorities. Institutions with an established Facilities and Administrative (F&A) rate should use their federally approved rate to calculate indirect costs for non-compute expenses.

What is the expected duration of the project?

The expected project duration is three years. Provide a timeline (Gantt chart) and milestones for each year of the three-year application. Milestones must be specific, quantifiable, and scientifically justified. 

Do one of the milestones have to focus on implementation and deployment of the technology?

Yes, at the level of demonstration, not validation. At the end of the three-year performance period, we expect demonstration in an appropriate mammalian animal model or human patients.

What are the important dates for the full application?

Applications must be submitted via Application Submission System & Interface for Submission Tracking (ASSIST) by March 7, 2025 at 5:00 pm (based on the local time of the applicant organization). Applications received past this date and time will not be accepted. 

Which applications will be reviewed? Which will not be reviewed?

Applications will only be accepted from entities listed in the Eligible Organizations section of this Announcement, who meet the criteria listed in the Eligibility Requirements. Applications submitted from organizations not included in the Eligibility section will not be reviewed. Applications that are deemed non-responsive or incomplete will not be reviewed.

How do I register to the NIH eRA Commons ASSIST system?

• Applicants must submit via the NIH eRA Commons ASSIST system no later than March 7, 2025 by 5:00 PM local time of applicant organization. Use RFA-RM-24-012 in the Funding Opportunity Announcement field. Here are instructions for submitting via the NIH eRA ASSIST system. Technical assistance is available from the eRA Service Desk.
• To submit a full application via ASSIST, the applicant organization must be registered in eRA Commons. If you are invited to submit a full application, you must be registered in eRA Commons, which may take six (6) weeks or more to complete, applicants should therefore begin the registration process as soon as possible.
• On the eRA Commons home page, select the “Register Organization” link for more details.
• To complete registration, if you have not done so already, you may need to register for the following:
  • System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
    • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. The same UEI must be used for all registrations, as well as on the other transactions application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission of the full application. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.
• If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance.

How do I submit my application?

All applications must be submitted electronically. Applicants should follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise [in this FOA (Section IV. Application and Submission Information) or in a Notice from NIH Guide for Grants and Contracts].

On what basis are applications selected for funding? 

Applications will be selected for funding based on scientific merit, current NIH program research priorities, and availability of funds. Applicants are highly encouraged to discuss potential research aims with program officials to determine fit with programmatic research priorities. 

Where will my application be reviewed? Is there any specific study section? 

Applications will be evaluated for scientific and technical merit via a special emphasis panel convened by the Center for Scientific Review in accordance with NIH peer review policy and procedures, using the stated review criteria. The assignment to a Scientific Review Group will be shown in the eRA Commons. 

Will NIH provide feedback on my application?

As part of the scientific peer review, all applications will receive a written critique in the form of a Summary Statement. NIH will not accept an appeal of the initial peer review or funding decision outcomes.

Do I need to show case in-vivo studies during the UH3 phase? Does it have be human studies? 

During the UH3 phase, applications will need to demonstrate the capability of the system for in-vivo imaging in either human or other mammalian animal models. Applicants proposing the use of non-mammalian tissue or non-mammalian organisms will not be considered responsive to the NOFO and the application will be withdrawn prior to review. 

Would I be eligible to apply if it becomes necessary to cut the tissue to increase the penetration depth of the optical imaging? 

The imaging modality should independently demonstrate its deep tissue imaging capabilities non-invasively, without requiring incisions or tissue perturbations. However, demonstrations conducted during surgical procedures, where tissue is already being incised as part of the operation, would also be acceptable. Applicants that propose a device that relies on surgical manipulation of the tissue and transgenic approaches to achieve increased imaging depth will not be considered and the application will be withdrawn prior to review. 

What wavelengths can be used for the imaging technology?  

Light in the ultraviolet to infrared range can be used. Applicants that propose the use of gamma-rays, x-rays, microwaves, or radio waves will not be considered responsive to the NOFO and the application will be withdrawn prior to review. 

How will projects be selected for the UH3 Phase? 

The Research Performance Progress Report submitted toward the end of year 2 will be reviewed administratively by NIH Program staff.  Projects must meet the stated milestones of the UG3 phase to be eligible for the UH3 Phase, for funding of the third and final budget period.   

How are Intellectual Property (IP) rights handled – is anything funded intended to be open access?

Generally speaking, any IP will be retained by the recipient, but NIH is granted licensing rights. Recipients of awards are expected to comply with NIH Data Sharing and Management Plans, Resource Sharing plans, comply with NIH Public Access policy, and report inventions in iEdison.  
For background regarding legislative authority concerning intellectual property rights: The Bayh–Dole Act is US legislation dealing with intellectual property arising from federally funded research. This Act encourages researchers to patent and market their inventions by guaranteeing patent rights. This Act automatically grants first rights to a patent for an invention fully or partially funded by a federal agency to the awardee organization. To obtain these benefits, however, the inventor and the organization have several reporting requirements that protect the rights of the government. For more information on the Bayh-Dole Act and NIH’s Role, please read Guide Notice NOT-95-003.

When will the first funding period open? 

We anticipate NIOI projects to be funded starting in FY26, with maximum 3-year project periods. The start date is anticipated to be no earlier than December 1, 2025, but no later than July 30, 2025. All key dates can be found on pp. 1 and 2 of the NOFO RFA-RM-24-012.

Are foreign partners allowed? 

Foreign partners are allowed as sub-awardees, but they cannot be the primary awardee. You must justify why the foreign partner brings a unique component that you would not find in the U.S.

Are industry partners encouraged?

Industry partners are encouraged. 

Is it mandatory to have partners from industry?

No, it is not mandatory, but we want to see an interdisciplinary team with expertise in all relevant areas of research and development included in the project, including commercial development. This does not have to necessarily come from industry partners if all components are met from academia or a non-profit organization.

What is the typical budget size for a team with one PI or a team with a PI and clinician?

The application budget should reflect the proposed activities and personnel. The awarded budget size is dependent on the objectives proposed in the application and subsequently determined prior to award issuance. 

Can a team be made up of industry partners only?

Yes. There is no requirement to make academic or non-profit partners a part of the team. Regardless of the make-up of the project team, applicants must demonstrate that they possess the experience and skillsets required to ensure success.

Are applications with multiple PIs permitted? 

Yes. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. Moreover, inclusion of PIs with diverse expertise (e.g engineering, biology, clinical) toward the completion of the aims of the projects are highly encouraged.  

Can an organization submit more than one application? 

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time. 

Can PIs submit multiple proposals?

PIs are welcome to submit multiple proposals so long as the scientific focus is unique for each proposal submitted. As such, the submission of multiple proposals is not encouraged or discouraged.

If we are not academic PIs, can we apply?

You do not have to be a part of academia to be eligible to apply. Academia, industry, and non-profit entities are eligible per the eligibility requirements stated in the NOFO. Individual persons cannot apply. 

Will I lose my early-stage investigator (ESI) or new investigator (NI) status for a future R01 submission for myself if I am awarded a grant under this NOFO? 

Yes, being awarded the UG3/UH3 NIOI will remove ESI and NI status for PDs/PIs because UG3/UH3 award is considered a substantial NIH independent research award. An ESI is a Program Director / Principal Investigator (PD/PI) who has completed their terminal research degree or end of post-graduate clinical training, whichever date is later, within the past 10 years and who has not previously competed successfully as PD/PI for a substantial NIH independent research award. A NI is a PD/PI who has not previously competed successfully for a substantial research award from NIH. See the list of NIH awards that a PD/PI can hold and still be considered an ESI or NI.   

Can we expect the same Venture initiative request for applications a year from now, or will the opportunity be issued only once?

We do not anticipate reissuing this NOFO next year. The NIOI initiative is a one-time opportunity that will fund projects in fiscal year 2026 with the level of funding in Year 2 and Year 3 contingent upon scientific progress and congressional appropriation of funding. If funding for awarded projects were to go beyond the three-year period, it would be through a different program at individual NIH ICs but not the Common Fund.

How many awards do you anticipate to fund?

We anticipate funding 3-4 awards in FY2026.

How can I follow the NIOI initiative?

Please consider signing up for the NIOI listserv. You can also follow the Common Fund X account for details about this initiative as well as other Common Fund programs: @NIH_CommonFund.

Are this initiative’s full application requirements similar to the standard R01 with respect to significance, innovation, and approach sections?

The RFA-RM-24-012 NOFO outlines the requirements for the full application.

How many specific aims would be appropriate?

This is completely dependent on the proposal. The proposed research activities will need to be commensurate with the budget request and within the 3-year period of performance.