Andrea Villanti, Ph.D. - US grants

DESCRIPTION (provided by applicant): Young adulthood (ages 18-24) is a critical developmental transition and provides an enormous opportunity to alter trajectories of smoking behavior for a large public health impact. Young adult smokers, in particular, have eluded both youth prevention and adult cessation intervention efforts. Recent increases in the rate of young adult smoking initiation and rate of transition to regular smoking have been reported along with the high prevalence of the phenomenon of social smoking in this age group (51%-62%). The long-term tobacco use behaviors of social smoking young adults (SSYAs) are unknown, but it is likely that approximately half will escalate to heavier cigarette use during young adulthood or that their pattern of social smoking will remain stable throughout adulthood. SSYAs present both a vital challenge and an opportunity for smoking cessation, but this requires a better understanding of potentially modifiable factors that contribute to risk. The current project uses primary socialization theory (PST) to address the intersection of social development and smoking behavior in young adulthood, identifying characteristics of and risk pathways leading from social smoking, a highly prevalent pattern of smoking among young adults. PST posits that individuals learn normative and deviant behavior mainly from a small number of social influences that change dynamically with lifespan transitions. The primary socialization influences in young adulthood are environmental (work, school), peer clusters, extended family, and the new family contexts created in this developmental period. The goal of the current study is to examine, in-depth, the characteristics of SSYAs, their potential smoking risk trajectories, and possible avenues for smoking cessation intervention. The proposal leverages information from two large contemporary cohorts of U.S. young adults (aged 18-24) with rich data on trajectories of cigarette smoking behavior, social influences on smoking, and social and contextual influences on in the moment smoking behavior among young adults. The two cohorts are: 1) a national sample of young adults aged 18-24 (n = 864 at baseline) Legacy Young Adult Cohort Study with semi- annual assessments over three years and 2) an at-risk group of adolescents followed during young adulthood (n = 1,027 at 5-year follow-up; NCI Program Project 2P01CA098262) using a combination of three annual assessments and two week-long sessions of daily ecological momentary assessment (EMA). Phase I of the study will use latent class analysis to define SSYAs in both cohorts (Aim 1) and Phase II will apply this definition to trajectory analyses in both cohorts, exploring tobacco use patterns among SSYAs compared to other young adult smokers (Aims 2 and 3). Phase III of the study takes a fine-grained approach to explore the proximal effect of social influences on smoking and cessation behavior and the potential of social smoking to serve as a moderator of this effect (Aim 4). This research lays the groundwork for developing more effective primary and secondary cancer prevention interventions for SSYAs by elucidating the social factors that maintain or impede smoking behavior in this important group.

PROJECT SUMMARY The wide range of tobacco and nicotine products available ? and the lack of education on these products ? has likely has left the public confused about the relative harms of tobacco products, and nicotine more generally. The extent to which young adults conflate the harms of nicotine with the harms of tobacco use could have beneficial or harmful effects at the population level. Young people who believe that all nicotine and tobacco products are equally harmful and addictive may avoid tobacco use altogether, more readily use the more satisfying and harmful combusted products, or fail to pursue evidence-based nicotine medications to assist in quitting tobacco use. Existing studies on tobacco-harm perceptions are largely cross-sectional and NIH-funded research on tobacco harm perceptions has focused on the tobacco products themselves without addressing perceptions of nicotine separately. Given the new tobacco marketplace and various forms of nicotine available to today?s consumers, there is an immediate need to: 1) understand the interplay between nicotine harm perceptions and tobacco product harm perceptions; and, 2) how these perceptions affect susceptibility to use tobacco and nicotine-containing products and ultimately tobacco use patterns in the population as a whole. The proposed study harnesses secondary analyses in longitudinal data from a large, national sample of U.S. young adults (n = 4,100 young adults aged 18-34) with novel measures of nicotine harm perceptions to produce an in-depth examination of the perceived harm of nicotine, the relative harm of tobacco products, and the impact of these perceptions on tobacco-related intentions and behavior. Quantitative analyses will: 1) examine perceptions of nicotine and relative harm of tobacco products in a national sample of U.S. young adults and correlates of these perceptions (e.g., sociodemographics, tobacco use); 2) characterize young adult subgroups based on their perceptions of nicotine and relative harm of tobacco products using latent class analysis; and 3) describe the impact of nicotine and tobacco harm perception ?class? on longitudinal patterns in susceptibility and curiosity to use tobacco and tobacco use behavior. Findings from this study are of particular importance given the imminent implementation of a required warning label (?This product contains nicotine. Nicotine is an addictive chemical.?) on tobacco products covered by FDA. The scientific premise of this study is that a better understanding of perceptions of nicotine and tobacco products will guide the development of more informative and effective tobacco product warning labels and other public education efforts.

PROJECT SUMMARY Recent changes in population patterns of tobacco use in youth and adults underscore the potential substitution of other menthol tobacco products for cigarettes in the face of a ban on menthol in cigarettes. The increased use of cigars and pipe tobacco in youth following the 2009 ban on flavored cigarettes is particularly important given that flavored filtered little cigars are often indistinguishable from cigarettes and flavored pipe tobacco can be used to make roll-your-own cigarettes. Mentholated pipe tobacco (for roll-your-own cigarettes, mRYO), menthol filtered little cigars (mFLC), and non-menthol cigarettes (nmC) appear to be plausible substitutes for menthol cigarettes. The goal of the current study is to examine the abuse liability and substitutability of these potential menthol cigarette substitutes using an in-laboratory and ad libitum outpatient mixed design. Eighty current menthol cigarette smokers (n=40 aged 18-24 years, n=40 aged 25+ years) will complete a three-phase study: in Phase 1, utilizing a randomized crossover design, participants' will complete 4 smoking sessions, smoking a different product each session to examine each product's abuse liability, demand, and topography. Products will include participants' usual brand menthol cigarette (UBMC) as well as 3 commercially-available alternatives, including mFLC, an mRYO product, and preferred non-mentholated cigarette (nmC). In Phase 2, to assess uptake, changes in subjective effects, and use over time, participants will select their preferred study product from Phase 1 and instructed to completely substitute the product for their UBMC for one week. Participants will complete ecological momentary assessments (EMA) during this period to more accurately assess substitution and perceived effects in real-time. In Phase 3, participants will complete a final in-lab visit to assess the substitutability of their preferred product from Phases 1 and 2, under simulated ban conditions using a progressive ratio task. In all phases, multiple domains of abuse liability will be assessed, including product administration (in-lab topography and EMA self-report measures), product liking/craving and withdrawal suppression (in-lab and EMA self-report). This study will be the first to estimate the substitutability of potential menthol cigarettes substitutes in adult smokers, which could impact the health benefit of a public health standard banning menthol in cigarettes. It will evaluate characteristics and perceptions (e.g., satisfaction, taste) of these products that may increase the likelihood of substitutability. Findings from this study will provide key information on the potential unintended consequences of a ban on menthol in cigarettes (i.e., the extent to which these substitutes would appeal to and be used by existing menthol cigarette smokers). They may also inform how FDA treats other non-cigarette tobacco products used as menthol cigarette substitutes in future proposed rulemaking, for example, extending the ban to menthol filtered little cigars or menthol pipe tobacco.

PROJECT SUMMARY ? Project 2 Smoking cessation in young adulthood is critical to preventing tobacco-related disease and death, particularly among socioeconomically-disadvantaged young adults (SDYAs) who are at greatest risk of tobacco-related health disparities. There are few efficacious smoking cessation interventions targeted to young adult (YA) smokers and while recent studies highlight that mobile and social media approaches to smoking cessation are acceptable to YA smokers, existing approaches are less effective in SDYA smokers. The overarching aim of the current study is to delineate how best to frame and deliver an efficacious smoking cessation intervention for SDYA smokers to improve cessation outcomes in this at-risk group. First, we will conduct formative research informed by behavioral economic theory on biases in decision-making to identify barriers to cessation, potential targets for cessation messages, and preferred mobile and social media modalities for smoking cessation intervention (e.g., text message, social media post, social media challenge) in SDYA smokers. Findings from this work will inform the development of themes/messages related to key drivers of smoking and barriers to cessation in SDYAs. Through iterative message testing, we will develop a library of cessation-related themes and messages for SDYAs that reflect the highest levels of personal relevance, likeability, and perceived effectiveness of messages. Our formative work will also inform a content delivery strategy (i.e., frequency of messaging, delivery of particular messages via text or social media, use of video and other creative content). Second, we will conduct a randomized controlled smoking cessation trial to test the efficacy of a tailored intervention for SDYA smokers using our curated content library and content delivery strategy. This work will concurrently build the evidence base on the distinct needs and challenges faced by SDYA smokers, while developing and testing smoking cessation intervention content uniquely relevant to this group. This study is aligned with two of the National Cancer Institute's tobacco control research priorities: 1) it addresses how tobacco interventions can be tailored or re-engineered to improve smoking-cessation outcomes in a group at particular risk for tobacco-related health disparities; and 2) it tests a novel intervention strategy to reduce young adult tobacco use that could be extended to other areas of cancer prevention in a low-cost, scalable format.

PROJECT SUMMARY The Society for Research on Nicotine and Tobacco (SRNT) is the only international scientific membership society dedicated exclusively to the field of nicotine and tobacco research. SRNT has more than 1,100 members from over 40 countries, with approximately 80 percent of those members being affiliated with U.S. research, advocacy, pharmaceutical and related organizations. The overall objective of the SRNT Annual Meeting is to stimulate advancement in the field of nicotine and tobacco research through presentation and discussion. It is the hallmark conference in the field where investigators, advocates, and policymakers can rapidly ?get smart? on the latest evolutions in the field, novel products in the marketplace, and effective interventions and policies to reduce tobacco use. The SRNT Annual Meeting has increasingly become the venue for presentation of novel findings from tobacco regulatory science research projects and networking across scientists in this emerging field. The aims of this conference grant are to: 1) ensure that tobacco regulatory science content is presented in ways that are maximally informative to FDA and to researchers in the field; and 2) to highlight the work of trainees and early career investigators in tobacco regulatory science via special oral sessions, professional development forums, travel awards, and other recognition. To meet both aims, SRNT?s Program Committee will meet regularly throughout the year to plan the content and format of the SRNT 2019 Annual Meeting, aligning the presentation of scientific content with research priorities in the Tobacco Regulatory Science Program (TRSP) and with FDA?s information requests via the public docket. The Committee will curate paper sessions on specific topics (e.g., flavors, nicotine reduction) that highlight advances in the area, foster scientific discussion and debate, and stimulate collaboration across researchers. The conference grant will also support 10 travel awards for trainees and early career investigators presenting on content related to the FDA and NIH Tobacco Regulatory Science Program research priorities. These interactions will facilitate the development of novel questions and approaches to tobacco regulatory science research.

PROJECT ABSTRACT FDA?s comprehensive plan on tobacco and nicotine regulation focuses on two key actions: 1) reducing nicotine levels in combustible cigarettes to make them minimally or non-addictive and 2) allowing for new forms of nicotine delivery to provide adult smokers with nicotine with lower resulting health harms than cigarettes. The public health impact of FDA?s proposed nicotine reduction policy hinge on the extent to which tobacco users and non-users understand the harms of nicotine in relation to specific products (e.g., e-cigarettes, nicotine replacement therapy (NRT), reduced nicotine content (RNC) cigarettes) and how this influences decisions made by non-users to try a product and by users regarding cessation, product switching, or continued use. Population data, including recent work by our group, highlight widespread public misperceptions of the health risks of nicotine that could undermine the public health benefits of FDA?s comprehensive plan. As a result, the introduction of FDA policies that reduce nicotine in some tobacco products while leaving it unregulated in others may require more nuanced public education about nicotine. Findings from our pilot work support that a brief nicotine corrective messaging intervention?similar to the messages likely to be seen on warning labels or in public education media campaigns?can correct misperceptions of nicotine, NRT, e-cigarettes, and RNC cigarettes in an online convenience sample of U.S. adults. The proposed study extends our pilot work to examine the effect of multiple exposures to nicotine corrective messaging (NCM) intervention (compared to a delayed intervention control) on nicotine beliefs and intention/use of tobacco and nicotine products in two parallel and complementary samples. A population-based study will estimate the potential public health impact of NCM on nicotine beliefs and tobacco- related behavioral intentions in 715 adult tobacco users and non-users, including potential unintended effects. A lab-based study will estimate the independent effects of NCM and RNC cigarettes, as well as their interaction, on nicotine beliefs and observed tobacco use behavior in 160 adult smokers who are explicitly told whether they have a normal nicotine content or RNC cigarette (i.e., unblinded). This study aims to provide insight into the real world impact of NCM communication efforts on tobacco use behavior in the general population and in adult smokers affected by a reduced nicotine content standard in combustible cigarettes. This study will test a set of evidence-based messages on nicotine, providing information on content and themes that could be used in future public education on nicotine to maximize the public health benefit of FDA?s comprehensive plan.

PROJECT ABSTRACT In the past six months, over 2,000 cases of vaping-related lung injury have been identified in 49 states, with 39 deaths. These injuries are taking a disproportionate toll on young people: the median age of these cases is 24 years and 54% of patients are youth or young adults under the age of 25. While evidence indicates that vaping THC plays a major role in this outbreak, the epidemic coincides with rapid increases in e-cigarette use in youth over the past two years. Time-sensitive information from young people on perceptions, patterns, and problems associated with vaping THC and nicotine is needed to guide state-level efforts. In the fall of 2019, the Vermont Department of Health launched the emergency Health Operations Center to track and respond to the state?s vaping-related lung injuries. As one of its early actions, the Center solicited data on vaping from the Policy and Communication Evaluation Study (PACE Vermont; www.pacevt.org), a six-month pilot study with quarterly online surveys in 1,500 youth and young adults completed in October 2019. The PACE Vermont Study is a partnership between the University of Vermont and the Vermont Department of Health to understand the impact of state-level policies and communication campaigns on substance use beliefs and behaviors in young Vermonters. This proposal continues the approach developed in the PACE Vermont Study to rapidly inform the VT HOC?s response to the outbreak of vaping-related lung injury. Expedited review and funding will allow for three additional waves of data collection in 1,500 Vermont youth and young adults to address questions raised by the VT HOC and the study team that would otherwise be impossible to obtain. Study aims address three areas: 1) changes in perceptions, patterns, and symptoms associated with vaping nicotine and marijuana in Vermont youth and young adults following the emergent outbreak of vaping-related lung injury; 2) characteristics of those who vape nicotine and marijuana, as well as those who report vaping-related symptoms or problems to guide intervention efforts; and 3) the impact of e-cigarette prevention messages on vaping-related harm perceptions and patterns of use. This proposal harnesses an experienced research team with expertise in rapid and responsive research, an established structure, and a community-engaged approach to address the rapid increase in vaping among young people and the emergence of vaping-related injuries. Partnership with the Vermont Department of Health and ongoing coordination with its emergency Health Operations Center ensures that data collected in this study will be rapidly incorporated into responses to these sudden and severe emerging drug issues in Vermont and potentially other states.

PROJECT SUMMARY The Society for Research on Nicotine and Tobacco (SRNT) is the only international scientific membership society dedicated exclusively to the field of nicotine and tobacco research. SRNT has more than 1,200 members from over 40 countries, with approximately 80 percent of those members being affiliated with U.S. research, advocacy, pharmaceutical and related organizations. The overall objective of the SRNT Annual Meeting is to stimulate advancement in the field of nicotine and tobacco research through presentation and discussion. It is the hallmark conference in the field where investigators, advocates, and policymakers can rapidly ?get smart? on the latest evolutions in the field, novel products in the marketplace, and effective interventions and policies to reduce tobacco use. The SRNT Annual Meeting is a unique venue for presentation of novel findings from tobacco regulatory science research projects and networking across scientists in this emerging field. The aims of this conference grant are to: 1) ensure that tobacco regulatory science content is presented in ways that are maximally informative to FDA and to researchers in the field; and 2) to highlight the work of trainees and early career investigators in tobacco regulatory science via special oral sessions, professional development forums, travel awards, and other recognition. To meet both aims, SRNT?s Program Committee will meet regularly throughout the year to plan the content and format of the SRNT 2020 Annual Meeting, aligning the presentation of scientific content with research priorities in the Tobacco Regulatory Science Program (TRSP) and with FDA?s information requests via the public docket. The Committee will curate paper sessions on specific topics (e.g., flavors, nicotine reduction) that highlight advances in the area, foster scientific discussion and debate, and stimulate collaboration across researchers. The conference grant will also support 10 travel awards for trainees and early career investigators presenting on content related to the FDA and NIH Tobacco Regulatory Science Program research priorities. These interactions will facilitate the development of novel questions and approaches to tobacco regulatory science research.

PROJECT ABSTRACT Coincident with the start of our project (R21DA051943), the COVID-19 pandemic dramatically altered the lives of youth and young adults. In Vermont, ?stay home, stay safe? orders were issued in March 2020, with schools closed for the remainder of the academic year and colleges transitioning to remote learning for the end of the spring semester. Disruptions in social interactions typical of adolescence and young adulthood may have resulted in reductions in peer and school influences that impact substance use; they may also have increased social isolation. Risks associated with reductions in these prosocial influences may be magnified by greater exposure to parental or household influences on substance use during this time. National studies document increases in mental health symptoms in response to COVID-related stressors, highlighting vulnerability for depression, anxiety, loneliness, and suicidality in young adults. Mental health symptoms, in turn, are correlated with tobacco and substance use in youth and adults. Preventing COVID-related morbidity and mortality in young people will require ongoing longitudinal tracking of mental health symptoms and rapid intervention to mitigate their effects on substance use. Our study embodies the infrastructure needed to achieve mental health and substance use surveillance and prevention goals. In line with the ?time sensitive? nature of the mechanism, we pivoted to add items on COVID-related experiences, distress, and the impact of the COVID-19 pandemic on substance use in the three survey waves in the parent study. This revision proposes three additional waves of data collection in 1,000 youth and young adults within the current project period to document the effects of the COVID-19 pandemic on youth and young adult mental health and substance use from Fall 2020 through Spring 2022. This timeline is also expected to span the release of a vaccine and greater return to in-person school and work. This supplement directly addresses the research priority in NOT-DA-20-047 to use ongoing studies to understand the broad impacts of COVID-19 on substance use: longitudinal surveys collected quarterly in a large sample of youth and young adults will provide fine-grained data on the relationship between COVID-related stressors, mental health, and substance use. Further, given Vermont?s rapid return to in-person school for youth and young adults in Fall 2020, data from this study will provide key information on the potential impact on young people of pandemic-related re-opening efforts across the country.