Millions of Americans use e-cigarettes. Despite their popularity, little is known about their health effects, and perceptions of potential risks and benefits of e-cigarette use vary widely among the public, users of e-cigarettes, health care providers, and the public health community. For example, whether e-cigarette use confers lower risk of addiction compared with combustible tobacco cigarettes is one point of controversy. Likewise, there are uncertainties about the harm of e-cigarettes themselves, because of the exposure to potentially toxic substances contained in e-cigarette emissions, especially in individuals, such as youth and young adults, who have never used tobacco products. Furthermore, concerns have been raised that e-cigarettes will induce youth to begin using combustible tobacco cigarettes. Given their relatively recent introduction, there has been little time for a scientific body of evidence to develop on the health effects of e-cigarettes. The purpose of this report is to (1) conduct a critical, objective, and evidence-based review of the scientific evidence that addresses the various competing views on the public health consequences of e-cigarettes; (2) make recommendations for the improvement of this research; and (3) highlight gaps that are a priority for future research.
STATEMENT OF TASK
The Consolidated Appropriations Act of 2016 includes language directing the Center for Tobacco Products (CTP) of the Food and Drug
Administration (FDA) to “contract with the Institute of Medicine1 to conduct an in-depth evaluation of available evidence of health effects from e-cigarettes and recommendations for future federally funded research” (U.S. Congress, 2016, p. 31). In accordance with this directive, CTP contracted with the National Academies of Sciences, Engineering, and Medicine to convene an ad hoc committee to conduct such an evaluation. (See Box 1-1 for the complete Statement of Task and Appendix A for a list of questions CTP provided for the committee to consider in addition to the Statement of Task.) The Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems includes experts in toxicology, nicotine pharmacology, adolescent and adult tobacco use patterns, epidemiology, public health, inhalation toxicology/pulmonology, cardiology,
1 As of March 2016, the Health and Medicine Division continues the consensus studies and convening activities previously undertaken by the Institute of Medicine (IOM).
pediatrics, obstetrics, and oncology (see Appendix F for the committee biosketches). The committee held five meetings, including a public workshop (see Appendix E for the public workshop agenda).
A NOTE ON TERMINOLOGY: WHAT ARE E-CIGARETTES?
E-cigarette products, their components, and their use lack standard nomenclature, and thus even manufacturers and users refer to them using different terms (Alexander et al., 2016). Throughout this report the committee uses the terms “electronic cigarettes” and “e-cigarettes” interchangeably to refer to any device with a heating element that produces an aerosol from a liquid that users can inhale. Characteristics of e-cigarette devices and products are described in more detail in Chapter 3. During a discussion at the first meeting, Mitchell Zeller, director of CTP, clarified that the use of the term “ENDS” in the Statement of Task does not refer exclusively to nicotine-containing e-cigarettes. Rather, CTP used the term to capture a heterogeneous group of products that are referred to using widely variable terminology. Thus, Zeller urged the committee to interpret the term broadly and not to limit the committee’s scope to nicotine-containing products, as e-liquids that do not contain nicotine or other substances made or derived from tobacco may still be subject to FDA’s tobacco control authorities. At the same time, a representative from CTP also noted that because CTP does not have regulatory authority over controlled substances such as marijuana, the committee should not focus on the effects of other controlled substances that could be consumed via an e-cigarette. Finally, Zeller also clarified that this class of products excludes electronic devices that do not contain liquids and instead heat tobacco, such as those referred to as “heat-not-burn” products. The committee’s use of the term e-cigarettes encompasses all products envisioned by CTP in the Statement of Task.
THE RAPID RISE OF E-CIGARETTE USE IN THE UNITED STATES
Several nationally representative surveys reported patterns of electronic cigarette use in the United States. These include three cross-sectional surveys with data on youth use, the National Youth Tobacco Survey (NYTS), Monitoring the Future (MTF), and Youth Risk Behavioral Surveillance (YRBS), and two cross-sectional surveys of adult use, the National Adult Tobacco Survey (NATS) and the National Health Interview Survey (NHIS). In addition, the Population Assessment of Tobacco and Health (PATH) study of youth and adults and the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) also provide longitudinal surveillance data. These surveys usually capture several measures of
e-cigarette use. Typical measures include ever use, current use, and frequent use. Ever or lifetime use captures whether an individual has used an electronic cigarette, even once or twice. Current use or use within the past 30 days typically captures whether someone has used an electronic cigarette on at least 1 day in the past 30 days. Frequent use generally describes e-cigarette use on 20 or more days of the past 30 days. Ever use is the most sensitive, but least specific, measure of use. Ever use collapses across low levels of use, such as experimentation (a temporary period of use that does not progress to regular or established use) and higher levels of use, including current, past 30-day, and frequent use. Cross-sectional data using such measures do not monitor patterns of use progression over time (trajectories), which leaves unclear whether people classified in one of these use patterns are on increasing, decreasing, or stable trajectories of use.
This section summarizes rates of electronic cigarette use as reported in these sources, including rates among subpopulations. Of note, although e-cigarettes entered the U.S. market in the middle of the first decade of the 2000s, little data on their use at a national level are available before 2011. Thus, little trend data are available even among surveys that collect data on e-cigarettes across multiple years. The lack of standard terminology also contributes to this problem because different surveys use different terms and definitions, and the terminology and definitions used to describe e-cigarettes across multiple years of the same survey change over time.
Youth Electronic Cigarette Use
Youth (age 17 and younger) have rapidly taken up e-cigarette use. The 2015 NYTS reported that 27.1 percent of middle and high school students ever used e-cigarettes (HHS, 2016b). Rates of ever use were similar in the 2016 MTF survey, ranging from 17.5 percent among 8th grade students to 29.0 percent among 10th graders, and 33.8 percent among high school seniors (Schulenberg et al., 2017). The most recent youth rates reported from the PATH survey (Wave 1 in 2013–2014) indicate much lower rates of ever use, with only 10.7 percent of youth ages 12 to 17 reporting ever using an e-cigarette even once or twice (Backinger, 2017). Conversely, rates in the 2015 YRBS are substantially higher, with 44.9 percent of high school students reporting ever using “electronic vapor products” (Kann et al., 2016). As can be seen, the proportion of youth who reported ever using e-cigarettes varies substantially across surveys. With respect to use in the past 30 days, the 2016 NYTS reported that 4.3 percent of middle school students and 11.3 percent of high school students reported any e-cigarette use in the past 30 days (Jamal et al., 2017). Table 1-1 shows
TABLE 1-1 Percentage of High School and Middle School Students Who Have Ever Used E-Cigarettes; National Youth Tobacco Survey (NYTS) 2011–2016
|% (95% CI)||% (95% CI)||% (95% CI)||% (95% CI)||% (95% CI)||% (95% CI)|
|High School||1.5 (1.2–2.0)||2.8 (2.3–3.5)||4.5 (3.8–5.3)||13.4 (11.2–16.1)||16.0 (14.1–18.0)||11.3 (9.9–12.9)|
|Middle School||0.6 (0.4–0.9)||1.1 (0.9–1.5)||1.1 (0.8–1.5)||3.9 (3.0–5.0)||5.3 (4.6–6.2)||4.3 (3.7–4.9)|
SOURCES: HHS, 2016b; Jamal et al., 2017.
the percentage of high school and middle school students who have ever used e-cigarettes, 2011 to 2016, in NYTS. MTF rates for 2016 are similar, with 6.2 percent of 8th graders, 11.0 percent of 10th graders, and 12.5 percent of 12th grade students reporting e-cigarette use in the past 30 days (Schulenberg et al., 2017). Again, youth use rates reported in the PATH Wave 1 survey in 2013–2014 are the lowest, with only 3.1 percent of youth age 12 to 17 reporting current use (Backinger, 2017), while rates among high school students in the 2015 YRBS are again the highest, at 24.1 percent (Kann et al., 2016).
Rates of frequent e-cigarette use among youth are quite low overall. The 2015 NYTS reported that 0.6 percent of all middle school students (comprising 11.7 percent of current middle school users) and 2.5 percent of all high school students (comprising 15.5 percent of current high school users) use e-cigarettes frequently (HHS, 2016b). Rates in PATH Wave 1 (2013–2014) among all youth age 12 to 17 are similarly low overall, at just 0.1 percent (Backinger, 2017).
As described above, little trend data are available. NYTS reports an increase in current use among middle schoolers from 0.6 percent in 2011 to a high of 5.3 percent in 2015, and among high schoolers from 1.5 percent in 2011 to 16.0 percent in 2015 (HHS, 2016b). Current use declined in 2016 to 4.3 percent among middle schoolers and 11.3 percent among high schoolers (Jamal et al., 2017). Due to changing terminology and definitions in MTF, it was only able to report trends from 2015 to 2016, but similar to NYTS, MTF reported a statistically significant decline in current use between these 2 years (Johnston et al., 2017). Trend data are not available for the YRBS or PATH.
Electronic cigarette use varies substantially across demographic subgroups, including age, gender, and race and ethnicity. In terms of age, e-cigarette use tends to increase with age among youth across all measures of use. For example, rates of ever, past 30-day, and frequent e-cigarette use are lower for middle school students compared with high school students in NYTS (HHS, 2016b; Jamal et al., 2017). Similarly, both ever and past 30-day use are lower in 8th compared with 10th and 12th and 10th compared with 12th grade students in MTF (Schulenberg et al., 2017). E-cigarette use also varies by gender, with typically greater use among boys than girls (Jamal et al., 2017). E-cigarette use also varies by race and ethnicity and generally is highest among youth who identify as Hispanic and non-Hispanic white (HHS, 2016b; Jamal et al., 2017).
In 2016, among youth who reported using tobacco, e-cigarettes were the most common form used. The 2016 MTF shows that 6.2 percent of 8th graders, 11.0 percent of 10th graders, and 12.5 percent of 12th graders reported e-cigarette use in the past 30 days (Schulenberg et al., 2017). This compares with 2.6 percent of 8th graders, 4.9 percent of 10th graders, and
10.5 percent of 12th graders reporting past 30-day combustible tobacco cigarette smoking (Schulenberg et al., 2017). Similarly, according to the 2016 NYTS, nearly double the number of middle school students (4.3 percent) reported currently using e-cigarettes compared with the next three products—combustible tobacco cigarettes, cigars, and smokeless tobacco (each at 2.2 percent), which were followed by hookah (2.0 percent), pipe tobacco (0.7 percent), and trailed by bidis (0.3 percent) (Jamal et al., 2017). Among high school students, 11.3 percent reported using e-cigarettes in the past 30 days, compared with only 8.0 percent combustible tobacco cigarette use, 7.7 percent cigar use, 5.8 percent smokeless tobacco use, 4.8 percent hookah use, 1.4 percent pipe tobacco use, and 0.5 percent bidi use. This pattern holds for all subgroups by race and ethnicity except among black middle and high school males who reported highest rates of cigar smoking followed by e-cigarette use (4.5 percent compared with 4.0 percent among middle schoolers and 9.5 percent compared with 6.2 percent among high schoolers) (Jamal et al., 2017).
Among those who reported having ever used an e-cigarette, youth most commonly reported using rechargeable/refillable tank-style devices, with more than half (53.4 percent) of middle and high school students reporting using only this kind of device (Singh et al., 2016). A total of 14.5 percent reported using only disposable models, and nearly one-third (32.1 percent) reported using both (Singh et al., 2016).
Even given the patterns of use described above, it remains unclear what precisely youth are vaping. Substantial proportions of youth report using non-nicotine electronic cigarettes. Among middle and high school students in the 2015 NYTS, nearly one-third (32.5 percent) of ever users of electronic cigarettes reported ever using an electronic cigarette device for any other substance other than for nicotine (Singh et al., 2016). Rates were similar among middle school students (33.7 percent) and high school students (32.2 percent). By contrast, analysis of the 2015 MTF found that nearly two-thirds of e-cigarette–ever users reported vaping “just flavoring” at last use. Again, rates were similar among 8th (66.0 percent), 10th (65.2 percent), and 12th (64.7 percent) grade students (CTP, 2017c). After “just flavoring,” e-cigarette–ever users of all ages next most commonly reported last vaping nicotine (22.2 percent among 12th grade students, 19.9 percent among 10th grade students, and 13.3 percent among 8th graders). Among ever users of all ages, roughly 6 percent reported vaping marijuana, and 13.7 percent of 8th graders, 7.7 percent of 10th graders, and 6.3 percent of 12th graders reported not knowing what they last vaped. Rates of last vaping just flavoring among past 30-day users are slightly lower compared with ever users, but still most common, except among 12th grade students who reported vaping six or more times in the past 30 days who most commonly vaped nicotine; 62.7 percent of 8th,
59.5 percent of 10th, and 59.2 percent of 12th graders reported last vaping just flavoring. After “just flavoring,” past 30-day vapers most commonly reported vaping nicotine (16.2 percent in 8th grade, 27.4 percent in 10th grade, 30.7 percent in 12th grade), followed by marijuana (10.6 percent in 8th grade, 8.75 percent in 10th grade, 5.2 percent in 12th grade), and don’t know (7.9 percent in 8th grade, 3.7 percent in 10th grade, 4.0 percent in 12th grade) (Miech et al., 2017).
Rates of e-cigarette use among adults (age 18 and older) are relatively low when compared with youth e-cigarette use and to adult combustible tobacco cigarette smoking. The 2014 NHIS survey reported that 12.6 percent of adults ever used e-cigarettes (Schoenborn and Gindi, 2015). The 2014–2015 TUS-CPS reported a substantially lower rate of ever use among adults, at 8.5 percent (Zhu et al., 2017). In terms of current (past 30-day) use, the PATH Wave 1 survey in 2013–2014 reported the highest rates of current use of e-cigarettes, at 5.5 percent (Coleman et al., 2017). NHIS data from 2014 show that 3.7 percent of adults reported currently using e-cigarettes (Schoenborn and Gindi, 2015). The rate of current use was lowest in the 2014–2015 TUS-CPS, at 2.4 percent (Zhu et al., 2017). According to PATH Wave 1 data, among current users, 21.3 percent reported daily use, 36.5 percent reported moderate use (more than 2 of the past 30 days), and 42.2 percent reported infrequent use (0 to 2 of the past 30 days) (Coleman et al., 2017).
Most adult e-cigarette users report currently using other tobacco products. According to data from Wave 1 of the PATH survey, among current users of e-cigarettes, 69.7 percent were current smokers, 8.6 percent quit smoking combustible tobacco cigarettes within the past year, and 5.7 percent were former smokers (abstained from smoking for more than 1 year) (Coleman et al., 2017). Interestingly, 16 percent of adult current users of e-cigarettes reported having never smoked combustible tobacco cigarettes. Additionally, 39.2 percent of current e-cigarette users reported current use of other combustible tobacco products (filtered cigars, cigarillos, traditional cigars, hookahs, and pipes) and 8.9 percent reported current use of non-combustible tobacco products (smokeless tobacco [snus pouches, loose snus, moist snuff, dip, spit, or chewing tobacco] and dis-solvable tobacco) (Coleman et al., 2017).
As with data on youth use, limited trend data are available on e-cigarette use among adults. MTF reported no significant change in ever use among college students from 2015 to 2016 (26.0 percent to 26.8 percent), a non-significant decrease in ever use among all young adults ages 19 to 30 (30.3 percent to 26.9 percent), a non-significant decrease in past
30-day use among college students from 8.8 percent to 6.9 percent, and a significant decrease in past 30-day use among all young adults (9.2 percent to 6.0 percent) (Schulenberg et al., 2017). These MTF data for young adults echo the decreases in youth use.
Among adults as among youth, patterns of use vary by demographic subgroups—age, gender, and race and ethnicity. With respect to age, e-cigarette use is generally greatest among young adults, and decreases with increasing age. According to 2016 MTF data, 26 percent of college students and young adults reported ever using electronic cigarettes, and 5.8 percent reported past 30-day use (Schulenberg et al., 2017). Past 30-day use is highest among those age 19 to 22 (8 percent) and declines steadily by age groups through those age 25 to 30 (Schulenberg et al., 2017). Similarly, the rate of ever use is highest among adults age 18 to 24 (21.6 percent), declining steadily with increased age in the 2014 NHIS (Schoenborn and Gindi, 2015). According to the 2013–2014 NATS, 35.8 percent of young adults age 18 to 24 reported ever using an electronic cigarette and 13.6 percent reported current use (HHS, 2016b). This compares with 16.4 percent of adults age 25 and older who reported ever using an e-cigarette and 5.7 percent who reported current use (HHS, 2016b). The PATH Wave 1 data on e-cigarette use also differ significantly by age for all use groups (daily, moderate, and frequent users) (Coleman et al., 2017). However, the PATH data show a slightly different pattern, with the highest use rates among adults age 25 to 34 (26.4 percent), followed by young adults age 18 to 24 (20.9 percent), and then decreasing with age among those 35 years and older.
Similar to youth use, differences in e-cigarette use among adults by gender typically show greater use among men compared with women. Significantly more men (14.2 percent) reported ever using electronic cigarettes compared with women (11.2 percent) in the 2014 NHIS data (Schoenborn and Gindi, 2015). In the PATH Wave 1 survey, current e-cigarette use was higher for men compared with women overall (53.5 percent compared with 46.5 percent, respectively). Among current users, use was also higher for men compared with women when stratified by intensity of use (daily, moderate, and infrequent use), but differences were not significant (Coleman et al., 2017). Similarly, according to the 2013–2014 NATS, among adults age 25 years and older, more men reported ever (18.3 percent), currently (6.6 percent), and frequently (23.0 percent among current users, 1.5 percent among all adults) using e-cigarettes than women (14.7 percent ever use, 5.0 percent current use, 20.6 percent frequent use among current users, and 1.0 percent current use among all adults) (HHS, 2016b).
Adult e-cigarette use also varies by racial and ethnic group. Data from the 2014 NHIS show that a significantly greater percentage of non-Hispanic whites (14.8 percent) reported ever using electronic cigarettes, followed by
Hispanic (8.6 percent), black (7.1 percent), and Asian (6.2 percent) adults. American Indian or Alaska Native (AI/AN) adults reported the highest rates of ever use, with greater than one in five reporting ever using e-cigarettes (Schoenborn and Gindi, 2015). Ever use of e-cigarettes was significantly higher among AIs/ANs compared with Hispanic, black, and Asian subgroups. PATH Wave 1 data (2013–2014) on current e-cigarette users show similar patterns by race and ethnicity. Among adult current users, significantly higher proportions of non-Hispanic whites (71.0 percent) currently use e-cigarettes, followed by Hispanics (12.7 percent), blacks (9.3 percent), those identifying as other race or multiracial (3.8 percent), and Asians (2.7 percent) (Coleman et al., 2017). Interestingly, in contrast to the highest rates of ever use among AIs/ANs in the NHIS data, rates of AI/AN current use from the PATH data are the lowest among all racial and ethnic subgroups, at only 0.6 percent (Coleman et al., 2017).
Among adults, device characteristics vary significantly by frequency of use. Among daily users, 73.6 percent used a refillable device and 91.6 percent used a rechargeable device (Coleman et al., 2017). Among those daily users who reported using a rechargeable device, only 42.3 percent reported use of cartridges. Among moderate e-cigarette users, 51.4 percent reported using a refillable device, 78.0 percent reported using a rechargeable device, and 61.5 percent of those using rechargeable devices reported using cartridges. By contrast, fewer than one-third (32.4 percent) of infrequent e-cigarette users reported using a refillable device and 58.6 percent reported using a rechargeable device; among those using rechargeable devices, 71.0 percent reported using cartridges. With respect to what substance adults are vaping, most adults reported vaping e-cigarettes that contain nicotine—91.2 percent of daily users, 88.2 percent of non-daily users, and 89.5 percent of both daily and non-daily users overall (Coleman et al., 2017). Approximately two-thirds of current users also reported using a non-tobacco flavored brand; these flavors include menthol, mint, clove, spice, candy, fruit, chocolate, alcohol (e.g., wine or cognac), or other sweet flavors (Coleman et al., 2017).
POTENTIAL PUBLIC HEALTH RISKS AND BENEFITS OF E-CIGARETTES
Electronic cigarettes contain constituents that are not inert and are likely to have some negative health effects on their own. Although toxic combustion products associated with cancers are less likely to be present, e-cigarettes emit potentially toxic substances including fine particulate matter, metals, and nicotine. These substances are known to cause adverse health consequences such as cardiovascular and respiratory illnesses. However, understanding the public health consequences of electronic cigarettes requires an understanding of the context of tobacco control
in the United States. Because e-cigarette use is understood not as a unitary and isolated phenomenon and because the known risks of combustible tobacco are so great, the net public health impact of e-cigarettes is expected to result from the effects of e-cigarette use on combustible tobacco cigarette smoking. Therefore, understanding the net public health effect of e-cigarettes requires understanding not only the inherent risks of e-cigarettes, but also the relationship between e-cigarette use and combustible tobacco cigarette use.
A central issue addressed in this report is the use of e-cigarettes as a harm-reduction tool, with a thorough evaluation of the evidence base for the hypothesis that electronic cigarettes are substantially less harmful and are a less toxic alternative to combustible tobacco cigarettes, because combustion, which produces substantial toxic substances, does not occur. Thus, among adult populations, to the extent that e-cigarette use promotes either reduction or complete abstinence from combustible tobacco smoking, e-cigarettes may help to reduce health risks. E-cigarettes could similarly reduce risks to youth who take up e-cigarettes instead of combustible tobacco cigarettes. This may be especially beneficial for certain vulnerable populations, such as pregnant women or smokers with physical (e.g., chronic respiratory or cardiovascular illness) or mental health comorbidities. Pregnancy is a vulnerable life stage because deleterious exposures to women during pregnancy may negatively impact child development (Bruin et al., 2010). Some evidence suggests that pregnant women increasingly switch from smoking combustible tobacco cigarettes to e-cigarettes because of their perceived lower harm (Bruin et al., 2010). This may bear out, but e-cigarettes also typically contain nicotine, which is known to harm child development (Bruin et al., 2010). Thus, the possible health effects of maternal e-cigarette exposure on the developing fetus remain unclear. Similarly, smokers with illnesses that could be caused or worsened by smoking, such as asthma, chronic obstructive pulmonary disease, cardiovascular disease, and cancer already experience heightened health risks of continued cigarette use. If e-cigarettes are effective for reducing or abstaining from combustible tobacco cigarette smoking, those with medical comorbidities may experience the greatest benefits from reducing their overall tobacco-related risks (Kruse et al., 2017). In these scenarios, the concern is the health effects of e-cigarettes compared with combustible tobacco cigarette use.
To the extent that laboratory tests of e-cigarette ingredients, in vitro toxicological tests, and short-term human studies suggest that e-cigarettes are likely less harmful than combustible tobacco cigarettes, due to lack of long-term epidemiological studies and large clinical trials, the implications for long-term effects on morbidity and mortality are not yet clear and the absolute safety of the products cannot be unambiguously assessed at this time and concerns about the uptake of e-cigarettes among youth and
young adults remain. Youth are a particularly vulnerable group, as they may be more likely to engage in risky behavior and experiment with illicit drugs and alcohol, and are differentially affected by nicotine or other toxicants throughout development (IOM, 2015). Thus, e-cigarette use among youth and young adults is especially worrying if e-cigarettes cause dependence or the normalization of smoking behavior, and subsequently lead youth and young adults to start smoking combustible tobacco cigarettes. This is of particular concern for youth who otherwise would never have smoked. Furthermore, concerns have been raised that e-cigarettes may deter current combustible tobacco cigarette smokers from quitting smoking or cause them to relapse. In these scenarios, the concern is the health effect of e-cigarettes (including transition to combustible tobacco cigarette use) compared with no use of either product.
In short, understanding the potential health risks and benefits of e-cigarettes requires an understanding of the risks of e-cigarettes relative to both cigarette smoke as well as never using any tobacco. Future regulatory strategies will determine whether the risks associated with electronic cigarettes (i.e., their potential to cause harm on their own, or through initiation of combustible tobacco cigarette smoking among individuals and populations) are sufficiently balanced with benefits (e.g., positive harm-reduction potential among individuals and populations).
The Family Smoking Prevention and Tobacco Control Act of 2009 (the Tobacco Control Act) granted FDA authority to regulate tobacco products manufactured, marketed, and distributed in the United States. While this included cigarettes, cigars, loose tobacco, and smokeless tobacco products, it did not include provisions specifically for electronic cigarettes. Rather, the law stated that any other tobacco products that the Secretary of Health and Human Services deems as relevant to the law may be included under FDA’s regulatory jurisdiction. Importantly, the Tobacco Control Act considers any product a “tobacco product” if it includes any constituent “made or derived from tobacco,” but is not otherwise regulated as a “drug,” “device,” or “combination product.”2 To regulate electronic cigarettes as tobacco products, FDA was required to undertake the rulemaking process. In May 2016, FDA published the final “deeming rule” (HHS, 2016a). Major provisions of the rule are listed in Box 1-2.
Given the possibility of pending product standards, marketing restrictions, and other regulations, the deeming rule has received both praise
2 Family Smoking Prevention and Tobacco Control Act of 2009, Public Law 111-31 § 906, 111th Cong. (June 22, 2009).
and criticism. Some scientific researchers believe the deeming rule can set in motion more rigorous and thoughtful research practices on e-cigarettes, thereby providing a strong evidence base for regulation and eventually reducing mortality from combustible tobacco product use (Backinger et al., 2016). Yet various stakeholders, including manufacturers, retailers, and consumers, are likely to hold different opinions about provisions in the deeming rule. For instance, under the deeming rule, anyone who “makes, modifies, mixes, manufactures, fabricates, assembles, processes, labels, repacks, relabels, or imports” any electronic cigarette product qualifies as a tobacco product “manufacturer,” and is therefore subject to the existing rules governing tobacco products (CTP, 2017c). Manufacturers will need to bear the burden of proof for their products to remain on the market after August 8, 2022, undergoing the premarket application submission process to obtain FDA authorization.
Given the regulatory hurdle, many independent manufacturers may not have the capital to remain in the market, whereas larger companies
will more easily overcome these financial barriers (Russell, 2016). Similarly, retailers may also feel encumbered by regulation, including restrictions on selling from vending machines, providing free samples, or selling any e-cigarette products or posting advertisements without visible and clear health warnings (CTP, 2017d). These regulatory changes may affect consumer behaviors. It has been suggested, for instance, that consumers may buy their current product of choice in bulk before it is removed from the market. Some may continue to buy products from an unlicensed vendor. Others still may begin mixing their own e-liquids at home, or begin smoking combustible tobacco cigarettes (Russell, 2016). Determining how manufacturers, retailers, and consumers will react to government policies is an important element in designing regulation and in predicting subsequent public health impacts.
The U.S. regulatory approach toward e-cigarettes is grounded in and shaped by its past regulation of tobacco, and other countries have followed different paths and arrived at very different approaches. Table 1-2 summarizes key events in the history of e-cigarette regulation in the United States. At least 68 different countries currently regulate e-cigarettes
TABLE 1-2 Summary of the Key Events in the History of E-Cigarette Regulation
|1964||Luther L. Terry, Surgeon General, releases first report of the Surgeon General’s Advisory Committee on Smoking and Health.a|
|1965||Herbert A. Gilbert’s patent request for an early approximation of an e-cigarette is approved on August 17.b|
|1992||Passage of the Synar Amendment to Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act on July 10 requires states to restrict sale and distribution of tobacco products to minors.c|
|Prescription nicotine patches are introduced to the U.S. market as smoking cessation aids.d|
|1995||FDA declares cigarettes “drug delivery devices” and proposes marketing and sales restrictions to reduce youth initiation.e|
|2000||On March 21, the Supreme Court affirms the 1998 court case ruling that FDA lacks the jurisdiction under the Federal Food, Drug, and Cosmetic Act to regulate tobacco. FDA subsequently revokes the final rule issued in 1995 as it is invalid.f|
|2003||Chinese pharmacist Hon Lik develops modern e-cigarette as it is currently known. It is entered into the market under the company Ruyan.g|
|2006||On August 22, the first import ruling in the U.S. Customs database appears. Electronic cigarettes have been officially introduced to the United States.h|
|2009||In April, FDA denies import of e-cigarettes and accessories, as products appear to be unapproved drug-delivery devices.i|
|In June, President Barack Obama signs the Family Smoking Prevention and Tobacco Control Act into law, giving FDA the authority to regulate tobacco products to protect public health. CTP is established; FDA announces a ban on combustible tobacco cigarettes with fruit, candy, or clove flavorings.j|
|2010||U.S. District Court for the District of Columbia enters judgment in favor of Smoking Everywhere and NJOY, ruling that e-cigarettes are not drug-delivery devices, as the intended use of e-cigarettes is to encourage nicotine use, not discourage, prevent, or mitigate.k|
|2011||On April 25, CTP issues a press release announcing its intention to regulate e-cigarettes as tobacco products.l|
|2016||On May 10, FDA issues final deeming rule: all products that meet definition of tobacco product (including e-cigarettes) are subject to CTP regulation.m|
|HHS releases the report E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General.m|
|2017||On July 28, FDA announces intentions to regulate nicotine levels in tobacco products.o|
NOTE: CTP = Center for Tobacco Products; FDA = Food and Drug Administration; HHS = Department of Health and Human Services.
c Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act of 1992, Public Law 102-321, 102nd Cong. (July 10, 1992).
i Smoking Everywhere, Inc., Sottera, Inc. and d/b/a NJOY v. U.S. Food and Drug Administration et al., 680 F. Supp. 2d 62 (D.C. Cir. 2010).
k Smoking Everywhere, Inc., Sottera, Inc. and d/b/a NJOY v. U.S. Food and Drug Administration et al., 680 F. Supp. 2d 62 (D.C. Cir. 2010).
in some fashion (Kennedy et al., 2017). Some policies are more permissive, such as in the United Kingdom, while others are more restrictive, such as in Australia. Implicit in many of the policies is an underlying assumption about the health effects of e-cigarette use, with the more permissive policies often based on the goal of maximizing the assumed health benefits of e-cigarette use and the more restrictive policies based on the goal of minimizing their assumed harm. An evaluation of the evidence on the health effects of e-cigarettes offers the opportunity to identify which harms and benefits are scientifically proven, which in turn would ultimately be the key outcomes to consider in evaluation of different e-cigarette policies and their population impact.
An important provision of the Tobacco Control Act is what is known as the public health standard. Unlike FDA regulation of pharmaceuticals under the standard of “safe and effective,” FDA regulates tobacco products based on a public health standard that considers the risks and benefits of the tobacco product on the population as a whole.3 Functionally, this means that FDA considers the effect of a tobacco product not only on those who use the product (e.g., smokers), but also on those who do not (e.g., people who have quit smoking combustible tobacco cigarettes but might relapse due to the presence on the market of a newly introduced product, or people who might begin to use tobacco who would not have otherwise). Products introduced onto the market after February 15, 2007 (such as most e-cigarettes) and products with a modified-risk claim must be shown to have a net population health benefit, for users and non-users of the product.
OUTLINE OF THE REPORT
Chapter 2 outlines the committee’s approach to identifying, reviewing, and assessing evidence on the effects of e-cigarettes on individual and population health. The report is then organized into three sections. The same standards of evidence assessment were applied to any outcome assessed, in all three sections of the report, so as not to give preference to harms or benefits. Section I includes three chapters reviewing the evidence on e-cigarette devices, constituents, and exposures. Section I ends with research recommendations related to those chapters. Section II begins with a chapter on modes of action of e-cigarette constituents and their relevance to human health. Seven chapters follow describing the evidence regarding the effects of e-cigarettes on human health, ranging from dependence to cardiovascular disease to burns from exploding
3 Family Smoking Prevention and Tobacco Control Act of 2009, Public Law 111-31 § 906, 111th Cong. (June 22, 2009).
device batteries. As shown in Appendix B, the committee did not limit its literature search to health outcomes that were “negative” or “harmful.” These chapters are not limited to comparisons with the effects of combustible tobacco cigarettes, and much of the literature assesses the effects of e-cigarette exposure independent of combustible tobacco exposure. Section II concludes with research recommendations. Section III addresses the public health implications of e-cigarettes, including chapters reviewing the evidence on the effects of e-cigarettes on youth initiation of combustible tobacco cigarettes, on adult cessation of combustible tobacco cigarettes, and on harm reduction, that is, a comparison between the effects of e-cigarettes and combustible tobacco cigarettes. A chapter using population dynamic modeling presents the results of a range of scenarios of the possible effects of e-cigarettes on a population measure of mortality (years of life lost) and reflects the range of conclusions relevant to the public health standard FDA is statutorily obligated to use in its regulatory decision making about tobacco products. Section III concludes with a chapter on research needs. The report ends with a chapter of brief concluding observations.
Alexander, J. P., B. N. Coleman, S. E. Johnson, G. K. Tessman, C. Tworek, and D. M. Dickinson. 2016. Smoke and vapor: Exploring the terminology landscape among electronic cigarette users. Tobacco Regulatory Science 2(3):204–213.
Backinger, C. L. 2017. Youth use of electronic cigarettes. http://c.ymcdn.com/sites/www. srnt.org/resource/resmgr/conferences/2017_annual_meeting/FDA_PreCon_Slides/Backinger_youth_e-cig_SRNT20.pdf (accessed September 18, 2017).
Backinger, C. L., H. Meissner, and D. L. Ashley. 2016. The FDA “deeming rule” and tobacco regulatory research. Tobacco Regulatory Science 2(3):290–293.
Bruin, J. E., H. C. Gerstein, and A. C. Holloway. 2010. Long-term consequences of fetal and neonatal nicotine exposure: A critical review. Toxicological Sciences 116(2):364–374.
CBP (U.S. Customs and Border Protection). 2006. NY M85579: The tariff classification of a nicotine inhaler and parts from China. https://rulings.cbp.gov/index.asp?ru=m85579&qu=NY+M85579&vw=detail (accessed September 18, 2017).
CDC (Centers for Disease Control and Prevention). 2009. History of the Surgeon General’s reports on smoking and health. https://www.cdc.gov/tobacco/data_statistics/sgr/history/index.htm (accessed September 18, 2017).
CDC. 2015. Highlights: Tobacco timeline. https://www.cdc.gov/tobacco/data_statistics/sgr/2000/highlights/historical/index.htm (accessed September 14, 2017).
Coleman, B. N., B. Rostron, S. E. Johnson, B. K. Ambrose, J. Pearson, C. A. Stanton, B. Wang, C. Delnevo, M. Bansal-Travers, H. L. Kimmel, M. L. Goniewicz, R. Niaura, D. Abrams, K. P. Conway, N. Borek, W. M. Compton, and A. Hyland. 2017. Electronic cigarette use among U.S. adults in the Population Assessment of Tobacco and Health (PATH) study, 2013–2014. Tobacco Control 26:e117–e126.
CTP (Center for Tobacco Products). 2011. Stakeholder letter: Regulation of e-cigarettes and other tobacco products. https://www.fda.gov/newsevents/publichealthfocus/ucm252360.htm (accessed September 18, 2017).
CTP. 2017a. Extension of certain tobacco product compliance deadlines related to the final deeming rule: Guidance for industry (revised). https://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM557716.pdf (accessed September 18, 2017).
CTP. 2017b. FDA announces comprehensive regulatory plan to shift trajectory of tobacco-related disease, death. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm568923.htm (accessed September 18, 2017).
CTP. 2017c. Manufacturing. https://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/Manufacturing/default.htm (accessed September 19, 2017).
CTP. 2017d. Summaryoffederalrulesfortobaccoretailers. https://www.fda.gov/TobaccoProducts/GuidanceComplianceRegulatoryInformation/Retail/ucm205021.htm (accessed September 19, 2017).
FDA (Food and Drug Administration). 2014. Significant dates in U.S. food and drug law history. https://www.fda.gov/aboutfda/whatwedo/history/milestones/ucm128305.htm (accessed September 14, 2017).
Gilbert, H. A., inventor. 1965. Smokeless non-tobacco cigarette. U.S. Patent 3,200,819. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=3200819.PN.&OS=PN/3200819&RS=PN/3200819 (accessed October 18, 2017).
HHS (U.S. Department of Health and Human Services). 2016a. Deeming tobacco products to be subject to the federal Food, Drug, and Cosmetic Act, as amended by the Family Smoking Prevention and Tobacco Control Act; restrictions on the sale and distribution of tobacco products and required warning statements for tobacco products. Federal Register 81(90):28973–29106.
HHS. 2016b. E-cigarette use among youth and young adults: A report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health.
IOM (Institute of Medicine). 2015. Public health implications of raising the minimum age of legal access to tobacco products. Washington, DC: The National Academies Press.
Jamal, A., A. Gentzke, S. Hu, K. A. Cullen, B. J. Apelberg, D. M. Homa, and B. A. King. 2017. Tobacco use among middle and high school students—United States, 2011–2016. Morbidity and Mortality Weekly Report 66(23):597–603.
Johnston, L. D., P. M. O’Malley, R. Miech, J. G. Bachman, and J. E. Schulenberg. 2017. Monitoring the Future national survey results on drug use, 1975–2016: Overview, key findings on adolescent drug use. Ann Arbor: Institute for Social Research, University of Michigan.
Kann, L., T. McManus, W. A. Harris, S. L. Shanklin, K. H. Flint, J. Hawkins, B. Queen, R. Lowry, E. O. Olsen, D. Chyen, L. Whittle, J. Thornton, C. Lim, Y. Yamakawa, N. Brener, and S. Zaza. 2016. Youth risk behavior surveillance—United States, 2015. Morbidity and Mortality Weekly Report 65(6):1–174.
Kennedy, R. D., A. Awopegba, E. De León, and J. E. Cohen. 2017. Global approaches to regulating electronic cigarettes. Tobacco Control 26(4):440–445.
Kruse, G. R., S. Kalkhoran, and N. A. Rigotti. 2017. Use of electronic cigarettes among U.S. adults with medical comorbidities. American Journal of Preventive Medicine 52(6):798–804.
Miech, R., M. E. Patrick, P. M. O’Malley, and L. D. Johnston. 2017. What are kids vaping? Results from a national survey of U.S. adolescents. Tobacco Control 26(4):386–391.
Pastore, M. N., Y. N. Kalia, M. Horstmann, and M. S. Roberts. 2015. Transdermal patches: History, development and pharmacology. British Journal of Pharmacology 172(9):2179–2209.
Russell, C. 2016. Unintended consequences of the FDA’s e-cigarette regulations. In The Hill: Capitol Hill Publishing Corp.
Schoenborn, C. A., and R. M. Gindi. 2015. Electronic cigarette use among adults: United States, 2014. NCHS Data Brief (217):1–8.
Schulenberg, J. E., L. D. Johnston, P. M. O’Malley, J. G. Bachman, R. Miech, and M. E. Patrick. 2017. 2016 Volume II: College students & adults ages 19–55. http://www.monitoringthefuture.org/pubs/monographs/mtf-vol2_2016.pdf (accessed September 18, 2017).
Singh, T., S. Kennedy, K. Marynak, A. Persoskie, P. Melstrom, and B. A. King. 2016. Characteristics of electronic cigarette use among middle and high school students—United States, 2015. Morbidity and Mortality Weekly Report 65(5051):1425–1429.
U.S. Congress. 2016. Division A-Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act, 2016. http://docs.house.gov/meetings/RU/RU00/20151216/104298/HMTG-114-RU00-20151216-SD002.pdf (accessed October 16, 2017).
Zhu, S. H., Y. L. Zhuang, S. Wong, S. E. Cummins, and G. J. Tedeschi. 2017. E-cigarette use and associated changes in population smoking cessation: Evidence from U.S. current population surveys. BMJ 358:j3262. https://doi.org/10.1136/bmj.j3262 (accessed February 6, 2018).