Key Dates

Related Announcements

NOT-OD-22-025 - Notice of Early Expiration of NOT-OD-21-137, Notice of Special Interest (NOSI): Electronic Nicotine Delivery Systems (ENDS) and Alternative Nicotine and Tobacco Delivery Systems: Population, Clinical and Applied Prevention Mechanisms of Health Effects

PA-18-592- Research Supplements to Promote Re-Entry into Biomedical and Behavioral Research Careers (Admin Supp - Clinical Trial Not Allowed)

PA-18-775 Pilot and Feasibility Studies in Preparation for Drug and Alcohol Abuse Prevention Trials (R34 Clinical Trial Optional)

PAR-19-274 - Dissemination and Implementation Research in Health (R01 Clinical Trial Optional)

PAR-19-275 - Dissemination and Implementation Research in Health (R21 Clinical Trial Optional)

PAR-19-276 - Dissemination and Implementation Research in Health (R03 Clinical Trial Not Allowed)

PAR-20-052 - NCI Small Grants Program for Cancer Research for Years 2020, 2021, and 2022 (NCI Omnibus R03 Clinical Trial Optional)

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-184 - Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-146 - NIDA Small Research Grant Program (R03 Clinical Trial Required)

PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

PAR-21-035 Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required)

PA-21-110 Pilot and Feasibility Studies in Preparation for Substance Use Prevention Trials (R34 Clinical Trial Optional)

PAR-21-190 - Modular R01s in Cancer Control and Population Sciences (R01 Clinical Trial Optional)

NOT-OD-21-114 - Notice of Intent to Reissue PAR-18-847 Electronic Nicotine Delivery Systems (ENDS): Population, Clinical and Applied Prevention Research (R01- Clinical Trial Optional) and PAR-18-848 (R21 - Clinical Trial Optional) as a Notice of Special Interest (NOSI)

Issued by

Division of Program Coordination, Planning and Strategic Initiatives, Office of Disease Prevention (ODP)

National Institute of Dental and Craniofacial Research (NIDCR)

National Institute on Drug Abuse (NIDA)

National Institute on Minority Health and Health Disparities (NIMHD)

National Cancer Institute (NCI)

Purpose

The Office of Disease Prevention and participating ICOs are issuing this Notice to communicate our interest in research on electronic nicotine delivery systems (ENDS). Research on alternative nicotine and tobacco delivery systems [e.g., heated tobacco products (also called heat-not-burn)] will also be considered. Research with a focus on other non-combustible nicotine and tobacco products will be considered on a case-by-case basis. Studies should examine population-based, clinical, and applied prevention of disease, including etiology and epidemiology of use, potential risks, benefits and impacts on other tobacco use behavior among different populations. Studies exclusively examining smokeless tobacco or combustible tobacco products (e.g., cigarettes, cigars) will be considered non-responsive.

Background:

Electronic Nicotine Delivery Systems (ENDS) are designed to heat a liquid solution, typically containing nicotine, into an aerosol to be inhaled by a user. ENDS represent a diverse class of products that include e-cigarettes, vapes, vaporizers, vape pens, hookah pens, and pods. In recent years, heated tobacco products, which do not involve combustion and are sometimes called heat-not-burn", have become available in the United States. For the purposes of this Notice, research examining products within the entire class of ENDS and heated tobacco products is sought. Other emerging non-combustible products will be considered on a case-by-case basis.

Adult prevalence of ENDS in 2019 was 4.5%, with young adults having the highest prevalence among all age groups (2020 Morbidity and Mortality Weekly Report). Current electronic cigarette use among young adults aged 18-24 increased from 7.6% in 2018 to 9.3% in 2019 (2019 Morbidity and Mortality Weekly Report). Youth ENDS use is also a significant concern. According to the 2020 National Youth Tobacco Survey, 20% (3 million) of high school students and 4.7% (550,000) of middle school students reported current e-cigarette use.

The tobacco product landscape is continuously changing. Despite rapidly accumulating research, significant gaps remain in our understanding of the public health effects posed by ENDS and heated tobacco products. More information is needed to understand the risk profile of the various devices or products and the aerosols they generate. The constantly changing landscape presents additional challenges for understanding how variable patterns of use and exposure to ENDS aerosol affect biological, physiological, and behavioral health outcomes. Research is needed to understand how ENDS product characteristics, product user characteristics, as well as the communication and policy environment interact to affect ENDS use patterns (e.g., exclusive use vs. dual use with combustible cigarettes). For example, although many adult smokers report using ENDS to help them quit smoking or to reduce their cigarette consumption, as noted in the 2020 Surgeon General’s Report on Smoking Cessation, there is presently inadequate evidence to conclude that e-cigarettes, in general, increase smoking cessation. These and other research gaps introduce challenges for accurate and meaningful communication about ENDS and heated tobacco products impact on an individual’s health. Applied, clinical, and population-based research studies provide a significant opportunity to address many unanswered questions and advance our understanding of their impact on public health.

Research Objectives:

This Notice encourages studies that seek to address gaps in our understanding related to population-based, clinical, and applied prevention research related to ENDS and heated tobacco products. The goal of these studies will be to better understand the impact of use of these products on the prevention of disease or the risk of disease (including cancer, dental, oral, and/or craniofacial). Increased comprehension about patterns of ENDS use with other tobacco products and how they affect addiction to nicotine, alcohol, and other drugs is sought, as well as understanding the effects of second- and third-hand exposure to the aerosols.

Research studies are also needed to assess the short- and long-term health effects of ENDS products and heated tobacco products across populations of special relevance. Research involving special populations such as, but not limited to, those listed below is encouraged:

• Persons with an existing disease or condition (e.g., cardiovascular disease, obesity, cancer, diabetes, mental health conditions, Alzheimer s, or related dementias) whose health outcomes could worsen due to ENDS use
• NIH-designated populations who experience health disparities in the United States [which include racial and ethnic minority groups (Blacks or African Americans, Hispanics or Latinos, American Indians and Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders), less privileged socioeconomic status, sexual and gender minorities, and underserved rural populations]
• Populations in communities with a high burden of tobacco-related health disparities (e.g., geographic regions like the Mississippi Delta or Appalachia, rural and urban neighborhoods, etc.)
• Persons with physical, developmental, or intellectual disabilities
• Underserved and vulnerable populations with increased patterns of ENDS and heated tobacco product use and/or addiction [e.g., adolescents (persons aged 10-19), youth (persons aged 15-24), pregnant people, etc.]

This NOSI encourages feasibility and pilot research, as well as efficacy and effectiveness research on new or adapted interventions. Observational, clinical and intervention human studies are appropriate. Research projects may also test new or adapted interventions, evaluate existing or ongoing community-based interventional programs or policies to generate significantly novel insights, or conduct dissemination and implementation research. Investigators must carefully review the specific priority areas of research for the NIH ICOs that are participating in this NOSI. Although areas of overlap among the ICOs exist, the specific research areas of interest for each participating NIH ICO are listed below.

Where appropriate, the standardized research e-cigarette (https://www.drugabuse.gov/funding/supplemental-information-nida-e-cig) should be considered for use in addressing specific research questions, or as a comparator for commercially available ENDS.

Investigators who conduct original and innovative basic biomedical, social, behavioral, clinical, or population-based research directed toward eliminating health disparities are invited to apply to this NOSI. Research shows that diverse teams working together outperform homogenous teams. Scientists and trainees from diverse backgrounds and with different life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. Diverse teams of scientists will lead the way to develop more innovative inclusive research that will more broadly enhance public health. Fostering diversity by addressing underrepresentation in the scientific research workforce is a key component of the NIH strategy to identify, develop, support, and maintain the quality of our scientific workforce. It is expected that research programs will include a diverse group of scientists, including individuals from underrepresented backgrounds as per NOT OD 20-031 (Notice of NIH's Interest in Diversity).

Study Design

Design, Analysis, and Sample Size Considerations for Studies to Evaluate Interventions:

Investigators seeking to evaluate the effect of an intervention on a health-related biomedical or behavioral outcome may propose a study design in which groups subjected to the intervention are compared to groups that are exposed to an appropriate comparison condition. The comparison condition should be justified based on the state-of-the-science for the intervention and the nature of the research question. Designs that might be proposed for studies that randomize groups or deliver interventions to groups include parallel group- or cluster-randomized trials, stepped-wedge group- or cluster- randomized trials, multiple baseline designs, and another quasi-experimental designs. Whenever participants are assigned in groups or clusters (e.g., families, clinics, schools, worksites, communities, counties, states), or participants receive some part of their intervention in a group or cluster, and observations on individual participants are analyzed for between-group effects, special methods are required for analysis and sample size. Applicants will need to show that their methods are appropriate given their plans for assignment of participants and delivery of interventions. Additional information is available at https://researchmethodsresources.nih.gov/.

Other Potential Study Designs: Randomized controlled trials may not be possible in all innovative research designs, e.g., where it is not possible to assign participants to high versus low discrimination condition or in small sample size communities where cross intervention contamination is likely to occur or be a problem. Alternative rigorous research designs that provide robust evidence of intervention effectiveness include quasi-experimental designs, such as multiple baseline or repeated measures design, interrupted time series design, or stepped-wedge cluster randomized designs in which all subjects receive the intervention. Further, hybrid effectiveness-implementation designs allow early observational investigation of implementation processes while also testing intervention effectiveness. Investigators should justify their research and analytic design selection and provide adequate evidence of their ability to execute a rigorous and appropriate analysis of randomized or non-randomized study data.

IC Specific Application and Submission Information:

Applicants must select the IC and associated FOA to use for submission of an application in response to this NOSI. The selection must align with the IC requirements listed in order to be considered responsive to that FOA. Non-responsive applications will be withdrawn from consideration for this initiative. In addition, applicants will be assigned to those ICs on this NOSI that have indicated those FOAs are acceptable and based on usual application-IC assignment practices.

• PA-20-183 -NIH Research Project Grant (Parent R01 Clinical Trial Required)
• PA-20-184 - NIH Research Project Grant (Parent R01 Basic Experimental Studies with Humans Required)
• PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-18-592 - Research Supplements to Promote Re-Entry into Biomedical and Behavioral Research Careers (Admin Supp - Clinical Trial Not Allowed)
• PA-20-194 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-196 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Basic Experimental Studies with Humans Required)

All instructions in the?SF424 (R&R) Application Guide?and the listed funding opportunity announcements must be followed, with the following additions:

• For funding consideration, applicants must include NOT-OD-21-137 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative. Studies exclusively examining smokeless tobacco or combustible tobacco products (e.g., cigarettes, cigars) will be considered non-responsive.

National Cancer Institute (NCI)

The National Cancer Institute encourages the submission of applications to fill gaps in the science regarding population, clinical and applied research on ENDS. Research on other emerging or novel nicotine and tobacco delivery systems, such as heated tobacco products (also called heat-not-burn) will also be considered. The NCI is interested in studies that investigate potential contributions to cancer risk from ENDS use alone or in combination with other tobacco products (dual/poly tobacco use). Of particular interest is research that seeks to better understand and prevent youth and young adult ENDS and heated tobacco product use, including initiation, escalation to regular use, dependence and studies that address ENDS cessation. This includes studies to identify the risk and protective factors that influence use patterns, and studies to understand trajectories of use, including intersection with other tobacco product use (e.g., cigarettes, cigars). Moreover, we encourage studies to understand the impact of communication and policy approaches (especially state and local policies) to address ENDS use, particularly among adolescents, young adults, and other populations that experience greater tobacco-related health disparities.

Specific topics of interest include but are not limited to:

• ENDS use among vulnerable populations and other populations that experience greater tobacco-related health disparities (e.g., youth, those with low SES, substance use and/or mental health issues, pregnant people, cancer patients and survivors)
• Risk and protective factors (e.g., parental influences, peer influences, proximity to tobacco and ENDS outlets and other environmental factors) for exclusive ENDS use and co-use with other tobacco products, cannabis and/or alcohol, particularly among youth and young adults
• How ENDS use influences smoking cessation (e.g., motivation to quit, quit attempts, sustained abstinence, and relapse)
• ENDS use behavior in former smokers, including continued use and/or relapse to smoking
• Effective approaches for ENDS cessation, especially to help youth and young adults quit exclusive ENDS use, as well as dual or poly use of ENDS with other tobacco products.
• Policies that impact ENDS use, such as smoke-free or ENDS-free laws, tobacco product price policies, school-based policies, and interactive effects of policies focused on ENDS with other tobacco control policies
• Clinical and other health care providers' advice and practice pertaining to ENDS, especially in cancer treatment settings
• Effective approaches for employing digital health technologies and social media to prevent ENDS use or deliver ENDS cessation programs
• Methods and measures of ENDS use that address heterogeneity of devices and characteristics and complexity in measurement of use behavior (e.g., frequency, intensity, and other aspects of use behavior)
• Studies to understand effects of heated tobacco product marketing on use behavior, particularly in young people and smokers who are motivated to quit.

NCI’s FOAs for this NOSI include the following or their subsequent reissued equivalents:

National Institute of Dental and Craniofacial Research (NIDCR)

NIDCR is interested in all applications within the scope of this FOA, that are relevant to the NIDCR mission and strategic plan. Specifically, there is an interest in ENDS (e-cigarettes) studies with a population, clinical, or prevention focus.

NIDCR is interested in studies that include but are not limited to:

• Feasibility and acceptability of ENDS prevention efforts in the dental setting
• Outcomes of ENDS prevention efforts currently conducted in the dental setting
• Epidemiology of ENDS, and dental, oral, and craniofacial diseases and conditions

Potential applicants are encouraged to speak with a NIDCR program official to discuss the relevance of proposed research topic(s). For additional information on the NIDCR mission and strategic plan, please see the NIDCR website: https://www.nidcr.nih.gov/ .

National Institute on Drug Abuse (NIDA)
NIDA is interested in supporting research to inform policy, improve practice, and advance addiction science. Studies of interest to NIDA include how ENDS affects nicotine addiction, particularly in relation to conventional tobacco or how ENDS use interacts with other substance use. Studies in vulnerable populations and those considered at risk for substance abuse are encouraged. Investigations that explore the role of genetics or epigenetics are also of interest. Research on alternative nicotine and tobacco delivery systems [e.g., heated tobacco products (also called heat-not-burn)] will also be considered.