Prioritizing Common Terminology and Measures to Advance Research on Oral Nicotine Product Use

Historically, oral nicotine products (ONPs) have included pharmaceutical nicotine replacement products (NRT) like nicotine gum or lozenges, which are approved by the U.S. Food & Drug Administration (FDA) Center for Drug Evaluation and Research for tobacco cessation, and conventional smokeless tobacco (SLT) products like chewing tobacco, moist snuff, or snus, which are regulated by FDA’s Center for Tobacco Products (CTP). A new oral tobacco product category recently emerged: ONPs, referred to by the industry as “modern” oral nicotine and often marketed as “tobacco-free.” ONPs are regulated by FDA’s CTP and are not FDA approved for tobacco cessation, and they primarily include nicotine pouches, lozenges, gummies, gum, and toothpicks. An evolving oral nicotine and tobacco product landscape presents measurement challenges and opportunities for tobacco regulatory science (TRS) and tobacco dependence treatment. The number and pace of new products entering the market entry demand continual market surveillance. Past experiences measuring e-cigarettes/vaping products, as they evolved, provide valuable lessons, demonstrating how ­tobacco researchers were slow to implement standardized terminology to refer to products and use.1,2 Common terminology and measures are deeply intertwined; if researchers use different terms, there will not be consistent measures to assess product use, determine product standards, or unravel population health effects. Additionally, common measures facilitate the assessment of patients seeking treatment for tobacco dependence. Currently, academics, scientists, and healthcare professionals lack a consistent approach for asking about ONPs and their use. This report recommends core measures to guide consistent measurement of ONP use by the scientific community; there is a particular focus on nicotine pouches due to their popularity relative to other ONPs.3 The Center for Coordination of Analytics, Science, Enhancement, and Logistics (CASEL) in TRS assembled a group of ONP researchers to develop recommendations for a core set of nicotine pouch measures for potential use across studies. First, we compiled existing measures of ONPs from national and international surveys, investigator-led projects, and published literature. By September 2022, over 170 self-report measures of ONP awareness, use, perceptions, attitudes, and beliefs were collected. Most measures (77%) were specific to nicotine pouches; fewer were about ONPs as an overarching product category (16%) or non-pouch ONPs (7%). The most common measures were about awareness and ever use. Yet, studies varied in how they operationalized the product as well as patterns of use and other domains (eg, reasons for use), limiting the ability to compare findings from different data sources. Indeed, measures of nicotine pouch use were included in 11 studies, but question phrasing differed each time. Measures typically followed a progression from awareness and ever use, to current or past 30-day use, and, finally, to established or regular use. Current or past-30-day use measures, which were identified frequently, capture a variety of behaviors including experimentation, occasional use, and regular use. Questions about first use and reasons for use, which were identified relatively ­infrequently in existing studies (perhaps because many surveys were not designed to reach people who use ONPs or to explore ONP use in-depth), have implications for addiction and health effects. Moreover, though ONPs come in discrete units, understanding nicotine delivery and/or toxicant exposure depends upon occasions of use, including how many are used per day and how long a product is kept in their mouth per use episode. In question prompts, ONP brand names were included more frequently than product images. Given the physical product similarities to conventional SLT/snus products and pharmaceutical NRT, question specificity is critical to measure use prevalence accurately. For example, nicotine pouches resemble SLT products in shape and packaging, as pouches have long been a popular traditional SLT style.3,4 Similarly, ONP gum, gummies, lozenges, and tablets often resemble FDA-approved NRT gum and lozenges, both in product formulation and channels for advertising (eg, television and radio).5 As such, ONPs may be mistaken for SLT or NRT or vice versa, making all measures of SLT, NRT, or ONP use susceptible to misclassification. Thus, a better understanding is needed of how consumers understand and use ONP product descriptors and terms. For instance, “tobacco-free” is frequently used in ONP marketing and may affect consumer risk perceptions.6,7 There are also nicotine-free herbal pouch products marketed with the term “tobacco-free” that have long been on the market, which may compound confusion. As such, common survey measures require clear operational definitions and product descriptions, which could be facilitated by including brand names and images.8 Although the behavior measures included in Table 1 have not been assessed formally for reliability or validity, they are nonetheless recommended to facilitate consistency across studies while important psychometric work is being conducted. At minimum, population surveys, clinical trials, and health records should include ONPs as a product category when assessing tobacco or nicotine use. When space allows, asking about flavors, nicotine strength, reasons, and occasions for use is important for understanding how product characteristics may influence use. While there are recommended core measures for assessing e-cigarette flavor use that may be applied to ONPs,9 questions assessing ONP flavors and nicotine strengths will need to be tailored to reflect the current market. In addition, basic survey principles, including product descriptions, use of popular brand names, and images, should be applied to increase understanding. Recommended Measures of Oral Nicotine Product (ONP) Use Recommended Measures of Oral Nicotine Product (ONP) Use A rapidly emerging market demands urgency in assembling a consistent measurement framework, but essential work on measurement reliability and validity is needed to support or recommend the use of optimal measures. A taxonomy covering ONPs, terms, and survey measures may be a logical next step.10 Future research should also consider the effects of question order—for example, should measures of ONP use go before or after traditional SLT? Until there is clear evidence for a recommendation, a detailed description of ONPs and how they differ from NRT, SLT, and snus may minimize this issue. More work also is needed on the flavor(s) and nicotine strength(s) of ONPs. Higher nicotine-strength pouches are becoming more common in the marketplace.11,12 Previous research suggests that many people who use e-cigarettes cannot accurately report e-liquid nicotine concentration, with some believing they are using zero nicotine when their liquid actually contains nicotine.13 Further, given recent federal, state, and local policies restricting sales of flavored tobacco products14 and FDA CTP’s authority to regulate non-tobacco (synthetic) nicotine products as of April 2022,15 it will be valuable to measure ONP flavor(s) and nicotine strength(s) to guide regulation. There is also a paucity of research examining knowledge, attitudes, motivation to use, and risk perceptions of ONPs. The rapidly evolving ONP market also highlights the need to consider nonsurvey data sources, such as retailer sales data (eg, Nielsen, IRI), that show which products are making an impact in which markets.7 Such data show that while the ONP category contains various products, the rapid growth of this market segment is driven largely by nicotine pouches.3 Importantly, market availability may differ from actual use patterns; though many ONPs are available, few brands have significant market share. In addition to retailer sales data, market expenditure data (eg, Kantar Media) can reveal how the industry promotes ONPs. For example, from January 2018 to April 2020, five pouch products (out of 22 ONPs advertised) accounted for 97% of ONP marketing expenditures, with the majority (61%) of advertising spending on television ads.5 Linking marketing expenditure data to national use data may help inform measure design. For instance, sales and marketing data may highlight important product characteristics for inclusion in survey measures (eg, packaging, flavor, nicotine strength). In addition to measures of use in population-based surveys, validated and standardized measures of dependence and subjective, pharmacokinetic, and pharmacodynamic effects are needed in clinical settings.16 New methods may be needed to measure the amount of nicotine delivered by ONPs and health effects more germane to these products. Clinical trials of smoking cessation/substitution should add ONPs as a category to other patient-reported outcomes (eg, timeline follow-back, ecological momentary assessment) to expand scientific evidence on use patterns (eg, dual use) beyond what can be collected by population surveys. Many ONPs are available today, with new brands and types continually emerging. With marketplace diversification, we need accurate and consistent measurement of product use to characterize the population impact of ONPs. Misclassification of ONPs to NRT and/or SLT/snus may bias prevalence estimates of product use and impact understanding of factors and conditions related to use. Similar concerns have been raised with inhalable, noncombustible nicotine products (eg, e-cigarettes, heated tobacco products),17,18 but the challenges of measuring ONPs have not been extensively acknowledged. High-priority research areas for ONP measure development reflect the many unanswered questions about ONP use. High-quality, independent data on nicotine/tobacco use patterns are important because these data often guide tobacco control and regulation. There is an urgent need to measure the use of this new product category, evaluate and establish the validity of ONP measures, and inform future research studies. Development and inclusion of standardized questions to measure ONP use, as well as knowledge, attitudes, motivation to use, and risk perceptions, are essential to understanding ONP use and their potential public health impact. This report is a cross-institution collaborative effort supported, in part, by the Center for Coordination of Analytics, Science, Enhancement and Logistics (CASEL) in Tobacco Regulatory Science U54DA046060-01 (National Institute of Drug Abuse [NIDA] and the Food and Drug Administration’s Center for Tobacco Products [FDA CTP]). Support for authors was also provided: MH and CDD were supported by the National Cancer Institute of the National Institutes of Health under U54CA229973 and U01CA278695. LF, MM, and SVJ were supported by NIDA under U54DA036151. SVJ was additionally supported by NIDA grant R56DA055996 (grant to Dr. Sven-Eric Jordt). BWC was supported by the National Heart, Lung, and Blood Institute under U54HL147127. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or U.S. Food and Drug Administration. We thank all the members of the tobacco regulatory science community who submitted oral nicotine product use measures to CASEL. LMF has received payment for serving on an advisory board for Imbrium Therapeutics, LLC. There are no other conflicts of interest to report. Mary Hrywna (Writing—original draft [Lead], Writing—review & editing [Equal]), Jenny Ozga (Project administration [Lead], Writing—review & editing [Equal]), Cassandra Stanton (Project administration [Supporting], Writing—review & editing [Equal]), Benjamin Chaffee (Writing—review & editing [Equal]), Cristine Delnevo (Writing—review & editing [Equal]), Lisa Fucito (Writing—review & editing [Equal]), Sairam Jabba (Writing—review & editing [Equal]), Meghan Morean (Writing—review & editing [Equal]), and Alayna Tackett (Writing—review & editing [Equal])