FAQs: High-Priority Research Topics R03 in Tobacco Regulatory Science

This is a critical question, as each of the specific aims in the application must meet the following criteria to be considered responsive. Each aim must:

• Address one or more of the High-Priority Research Topics listed in the NOFO.
• Fall within the scope of FDA CTP’s regulatory authority.

Applicants are strongly encouraged to contact the Scientific/Research Contact(s) listed in the NOFO for feedback on responsiveness before submitting an application. Sharing your research ideas and specific aims and submitting a letter of intent before applying allows NIH staff to provide feedback on responsiveness.

If your application is deemed responsive, it will undergo scientific peer review by experts convened specifically for this request for applications (RFA) by the NIH Center for Scientific Review (i.e., a Special Emphasis Panel). If your application is deemed non-responsive, it will be withdrawn before it is evaluated for scientific merit (i.e., peer review). Program officials will let you know if the application has been withdrawn from peer review.

This NOFO has two application due dates: November 18, 2025, and July 14, 2026. The NOFO will expire on July 15, 2026.

Currently, all other open Tobacco Regulatory Science Program (TRSP) NOFOs specify similar (or the same) High-Priority Research Topics. Therefore, we recommend contacting program officials at the NIH institutes and centers (ICs) named in the RFA to determine whether your proposal fits within their IC’s current mission and priorities. Program officials may also suggest that you speak with other program officials at non-participating ICs.

No. Although the two lists of High-Priority Research Topics are similar, the topics under “High-Priority Research Relevant to Product Composition and Design” and “High-Priority Research Relevant to Toxicity” in the R03 RFA (RFA-OD-25-008) differ from those listed in the expired R01 RFA (RFA-OD-25-001). The topics listed in the R03 RFA are more specific to account for the smaller budget of an R03 project. 

NI status is only applicable if you have not yet successfully competed for a substantial NIH independent research award. For a list of awards that are excluded from consideration as “independent research,” see the definition of New Investigator. Although PD/PIs of an R03, R21, or R00 award are generally considered to have NI status, note that this NOFO excludes from consideration individuals who have received a Small Grant Program Award (R03) or an Exploratory/Developmental Research Grant Award (R21) funded through the FDA CTP, as well as those who are in the Research Award Phase (R00) of a Pathway to Independence Award funded by the FDA CTP. This includes recipients supported through the following NOFOs:

• Research Award Phase (R00) of a Pathway to Independence Award in Tobacco Regulatory Research (K99/R00 - Independent Clinical Trial Not Allowed)
• Research Award Phase (R00) of a Pathway to Independence Award in Tobacco Regulatory Research (K99/R00 - Independent Clinical Trial Required)
• Tobacco Regulatory Science Small Grant Program for New Investigators (R03 Clinical Trial Optional)
• Tobacco Regulatory Science Exploratory/Developmental Research Grant (R21)

Investigators who have questions about eligibility should contact the Scientific/Research Contact(s) listed in Section VII. Agency Contacts of the NOFO.

Yes. NI status is initially based on the investigator’s status on the date the application is successfully submitted to NIH. However, NI status will be reassessed after peer review and before consideration for award to identify if other pending applications exist. A principal investigator (PI) will lose NI status immediately upon receipt of any substantial NIH research grant, so receipt of an R01 prior to the notice of award for this RFA would make you ineligible.

Yes. Investigators who have been an independent PD/PI on a Small Research Grant Program (R03) are not eligible to apply for a Pathway to Independence Award (K99/R00).

Yes, you can see whether you are currently designated as an NI in your eRA Commons account. NI status is determined automatically by the functionality built into eRA Commons based on the investigator’s record of awarded NIH grants. For instructions on getting an eRA Commons account, which is required before submitting an application, see Create and Manage an eRA Commons Account on the NIH eRA website. In addition to this function that automatically determines NI status, NI status also is impacted by whether you have previously received a CTP-funded award (as stated more thoroughly in the first Q&A in the Eligibility section).

If you believe that your designation doesn’t reflect your current NI status, you can “Submit a Web Ticket” to the eRA Service Desk to request a correction to NI status for the submitted application. 

To check if you are correctly designated as an NI or Early Stage Investigator, log into your eRA Commons account and confirm that your Personal Profile indicates the correct status.

No, this is an independent research award.

No, foreign institutions are not eligible to apply for this R03.

The intent of this RFA is to develop a cadre of NIs in the early stages of establishing independent careers in tobacco regulatory research. There are no citizenship requirements to apply, but investigators must demonstrate that the proposed research can directly contribute to FDA CTP’s regulatory authority over tobacco products and to one or more of the High-Priority Research Topic(s) listed in the RFA. Individuals also must demonstrate that they will be employed by an eligible institution for the full award period of the grant.

Yes. R03 budgets submitted to this NOFO (RFA-OD-25-008) are limited to $75,000 in direct costs per year. Budgets exceeding this cap will not be considered.

An LOI is not required and is not part of the peer-review process. However, LOIs allow NIH staff to estimate the potential review workload and plan the review. Investigators are encouraged to submit specific aims with their LOI to allow NIH Scientific/Research Contact(s) to review their research ideas and aims before the applications are submitted because all specific aims must be within the regulatory authority of FDA CTP and clearly address one or more of the NOFO’s High-Priority Research Topic(s) to be deemed responsive. Applications that are non-responsive will not be reviewed. To ensure timely feedback on the responsiveness of specific aims, please submit LOIs no later than September 18, 2025, for the November 18, 2025, application due date and May 14, 2026, for the July 14, 2026, application due date.

Suggested LOI content:

• A descriptive title of the proposed activity
• Name(s), address(es), and telephone number(s) of the PD/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity
• Specific aims

The LOI may be emailed to [email protected].

Only the High-Priority Research Topics listed in the NOFO will be deemed responsive. Although the following research topics may be fundable within FDA CTP’s regulatory authorities, they are not included in this NOFO and will be deemed non-responsive:

• Investigations of tobacco products other than those explicitly specified in the High-Priority Research Topics of the R03 RFA
• Studies exploring how to effectively communicate to the public regarding nicotine and the health effects of tobacco products through media campaigns and digital media
• Studies exploring the impact of marketing on susceptibility to and initiation of using tobacco products (both classes of products and products within classes) and transitions between experimentation, initiation, regular use, product switching, dual use, and cessation-related behaviors among different populations
• Studies of the potential or actual impact of FDA regulatory actions
• Mechanistic studies (i.e., basic science of disease development), unless biomarkers of harm with predictive value for disease development associated with tobacco product use is included as an outcome
• Short-term studies of the acute effects of reduced nicotine content cigarettes
• Studies identifying biomarkers of secondary and tertiary exposure to tobacco products
• Studies of in utero exposure to tobacco products and subsequent behavioral effects in offspring
• Studies using neuroimaging as a biomarker of tobacco product exposure or nicotine dependence
• Studies identifying epigenetic biomarkers associated with tobacco use, including DNA methylation or other non-DNA sequence–related mechanisms that regulate gene expression through such reversible alterations as histone modification and non-coding RNA modulation

For example, is a proposed longitudinal study focusing on perceptions of, use behavior of, and dependence on heated tobacco products responsive to this RFA even though heated tobacco products are not listed as a product of interest in the addiction research topic?

If the study of heated tobacco product dependence is related to the use behaviors of the product, then the proposal may be considered responsive under the High-Priority Research Topic relevant to behavior. The proposal may be considered non-responsive if it were seeking to respond to the High-Priority Research Topic relevant to addiction for any product other than electronic nicotine delivery systems (ENDS) and/or nicotine pouches. As the determination of responsiveness will be dependent on the details of the proposal, we strongly recommend discussing your specific aims with the Scientific/Research Contact(s) listed in the RFA before submitting an application.

No, cancer in human subjects is not responsive to this RFA (RFA-OD-25-008). The High-Priority Research Topic is seeking to understand the non-cancerous pulmonary effects of ENDS. As stated in the RFA, research on the impact of ENDS use on human health is limited to cardiovascular, pulmonary effects, or neurological health effects, including acute and/or chronic health outcomes in human subjects (i.e., not animal models).

No, cognitive function is not responsive to this RFA. However, examples of outcomes that would be responsive to neurological effects of ENDS may include stroke, seizures, or other acute and/or chronic health outcomes in human subjects.

No. A study with cannabis/marijuana as one of the primary outcomes is not responsive because FDA CTP does not regulate cannabis/marijuana under its tobacco product authorities. However, research designed to evaluate the extent to which cannabis/marijuana is used within tobacco products (e.g., within nicotine-containing e-cigarettes or blunts) as a means to more accurately characterize or assess tobacco product use behavior could be responsive to FDA CTP authorities.

No. Studies proposing to focus on products that do not contain nicotine or tobacco-derived constituents but instead contain nicotine analogs (e.g., 6-methyl nicotine) are not responsive to this RFA. However, studies that analyze tobacco products (i.e., those containing nicotine or tobacco-derived constituents) for the presence or absence of nicotine analogs (e.g., 6-methyl nicotine) when characterizing product composition may be responsive. Please note that such proposed research should be confirmed for responsiveness by the Scientific/Research Contact(s) listed in the RFA prior to application submission.

Potentially, yes. If the product(s) meets the statutory definition of a “tobacco product” under the Tobacco Control Act (i.e., any product made or derived from tobacco or containing nicotine from any source that is intended for human consumption, including any component, part, or accessory of a tobacco product), then studies examining these products could be considered responsive if they address one or more of the High-Priority Research Topic(s). However, the application must demonstrate that the proposed research can directly contribute to FDA CTP’s regulatory authority over tobacco products within the United States. Note that some of the High-Priority Research Topics in this NOFO specify the type(s) of tobacco products to be studied. Therefore, the proposed research must clearly address the type(s) of tobacco products stated in the NOFO given the High-Priority Research Topic(s) that the proposed research plans to address.

Yes, foreign populations may be included in the proposed research. However, results from research in foreign populations must be relevant to the U.S. population and U.S. regulation of tobacco products. For example, studies assessing health effects related to tobacco product use would be relevant to the extent that the findings could be generalized to the United States. Studies assessing general knowledge or attitudes about tobacco products among foreign populations likely would not be relevant.

Per the NIH notice (NOT-OD-25-104) published on May 1, 2025, foreign subawards are no longer allowed. However, the notice states that while this policy applies to all monetary foreign collaborations, “it does not apply to funds provided to support foreign consultants.” For the definition of a consultant, please see the NIH Grants Policy Statement. Additionally, you may also refer to NIH policy and compliance information on subawards, which includes a section on foreign subawards. Please note that some websites may have yet to be updated to reflect the notice on foreign subawards (NOT-OD-25-104).

As stated in NOT-OD-25-104, “Notices of Funding Opportunities (NOFOs) that state that foreign components are allowed are superseded by this notice.” In other words, the notice supersedes the text in the RFA regarding foreign organizations and foreign components.

Yes, studies in populations experiencing tobacco-related disparities are responsive to FDA CTP regulatory authorities. However, the population needs to be appropriate for the research question. If a population experiencing tobacco-related disparities will be included, applicants will be expected to identify the population and how it is important to the research question, considering the impact on population health.

Yes. The PI may resubmit an application by the second and last submission date for this RFA. It is highly recommended that the PI address all the issues and concerns raised in the summary statement from the peer review.