The fact that daily ecig users quit more is not relevant to FDA CTP’s assessment of whether to authorize the sale of e-cigs

The new paper “Association of e-cigarette use with discontinuation of cigarette smokers among adult cigarette smokers who were initially planning to quit” in JAMA Open Network by Karin Karza and colleagues confirms that smokers who use e-cigarettes daily are more likely to quit cigarettes than those who don’t use e-cigarettes. Also consistent with earlier studies, it also found that nondaily e-cigarette users were less likely to quit cigarettes, although this effect did not reach statistical significance, probably due to small numbers.

As shown in the graph above from our meta-analysis of e-cigarettes and quitting cigarettes (which is based on the literature as of January 2020), smokers who use e-cigarettes daily are significantly more likely to quit smoking than smokers who don’t use e-cigarettes. Non-daily e-cigarette users are significantly less likely to quit. Indeed, the adjusted odds of quitting Karza et al report for nondaily e-cig users, 0.53, is almost identical to the 0.51 that we found in our meta-analysis.

So, this confirmatory analysis doesn’t add much new to the literature but rather reinforces existing understanding based on longitudinal data. The one big limitation of the paper is the small number of actual cigarette quitters — 3 among the nondaily e-cig group and 17 among the daily group. The reason for these small numbers is that the authors were limiting themselves to daily smokers who specifically expressed no interest in quitting smoking at baseline combined with the usual loss to follow-up in longitudinal studies. That is also why the confidence intervals in this study are quite wide.

My concern with the paper is what they conclude in terms of regulatory implications when they write

This cohort study found an association between daily e-cigarette use and cigarette discontinuation among daily smokers in the US population who initially had no plans to ever quit smoking in their lifetimes. These findings call for consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population. Further, given the growing popularity of e-cigarettes in the US, and considering smokers’ very low interest in using traditional smoking cessation medications, future research into the comparative reach and effectiveness of different types of products will be important to informing clinical and regulatory strategies to increase cigarette discontinuation rates at the population level. [emphasis added]

This statement does not consider the fact that, unlike the FDA Center for Drug Evaluation and Research (CEDR) which approves prescription drugs and which can specify how they are to be used, the FDA Center for Tobacco Products (CTP) has no authority to specify how e-cigarettes are used.

Unlike CDER, which can require a prescription to obtain drugs under specified circumstances to be dosed in specified ways, all CTP can do is allow or deny authorization to sell the products to any adult who wants them. Indeed, the Family Smoking Prevention and Tobacco Control Act that gave FDA authority over tobacco products, including e-cigarettes as consumer products, specifically forbids CTP from requiring that any tobacco product it regulates from requiring a prescription. Thus, the appropriate number for consideration is how e-cigarettes as actually used in the entire population — regardless of whether someone is a daily or nondaily user — affects cigarette cessation.

Karza and colleagues did not report that number in their paper. One can estimate what it would be by computing the weighted average of daily (28% of users in their study) and nondaily (72%) e-cig use using a fixed effects meta-analysis. The result is an overall nonsignificant odds of quitting of 1.15 (95% CI 0.29-4.49), also consistent with our earlier meta-analysis finding no significant association between e-cigarette use and adult smoking cessation. Read in that context, Karza et al add to the case the e-cigarettes as population interventions do not help adult smokers quit.

It is also important to note that most (72%) of the e-cigarette users they studied were non-daily e-cigarette users. So even if one takes their finding of a nonsignificant effect on smoking cessation at face value, there is no benefit for the great majority of smokers they studied. And, as noted above, their point estimate is also consistent with the meta-analysis of the larger literature showing less quitting among non-daily e-cig users.

Of course, if tobacco/e-cigarette companies submitted their products to CEDR (as opposed to CTP) for approval as drugs to be prescribed to an identified group of smokers, then the dosing information in this paper would be highly relevant.

Health researchers studying e-cigs and smoking cessation need to pay attention to the fact that CTP is not CDER and plays by different rules — particularly what CTP is and is not allowed to do — when discussing the policy implications of their findings.

Here is the abstract:

Importance  Cigarette smokers not planning to quit are often overlooked in population studies evaluating the risk-benefit potential of electronic nicotine delivery products (e-cigarettes).

Objective  To evaluate whether e-cigarette use is associated with discontinuing cigarette smoking among smokers who were initially never planning to quit.

Design, Setting, and Participants  This cohort study used US nationally representative data from the longitudinal Population Assessment of Tobacco and Health Study (waves 2-5 conducted between October 2014 and November 2019), with participants evaluated in 3 pairs of interviews. Adult daily cigarette smokers initially not using e-cigarettes and with no plans to ever quit smoking for good (2489 observations from 1600 individuals) were included.

Exposures  e-Cigarette use (ie, daily use, nondaily use, or no use) at follow-up interview among smokers not using e-cigarettes at baseline interview.

Main Outcomes and Measures  The main outcomes were discontinuation of cigarette smoking (ie, no cigarette smoking) and discontinuation of daily cigarette smoking (ie, no daily cigarette smoking) at follow-up interview. Generalized estimating equations were used to evaluate the association between the exposure and each outcome, controlling for demographic characteristics and cigarettes smoked per day at baseline interview; all estimates were weighted.

Results  The weighted population of adult daily cigarette smokers who were not using e-cigarettes and had no plans to ever quit smoking, based on data from 1600 participants, was 56.1% male (95% CI, 53.4%-58.7%), 10.1% Hispanic (95% CI, 8.2%-12.3%), 10.1% non-Hispanic Black (95% CI, 8.7%-11.7%), 75.6% non-Hispanic White (95% CI, 72.9%-78.2%), and 4.2% of other non-Hispanic race (95% CI, 3.3%-5.4%); 29.3% were aged 55 to 69 years (95% CI, 26.2%-32.6%), 8.9% were aged 70 years or older (95% CI, 6.8%-11.5%), 36.8% did not graduate from high school (95% CI, 34.1%-39.6%), 55.2% had an annual household income of less than $25 000 (95% CI, 52.3%-58.1%), 37.6% smoked 20 to 29 cigarettes per day (95% CI, 34.7%-40.6%), and 12.7% smoked 30 or more cigarettes per day (95% CI, 10.9%-14.7%). Overall, 6.2% of the population (95% CI, 5.0%-7.5%) discontinued cigarette smoking. Discontinuation rates were higher among those who used e-cigarettes daily (28.0%; 95% CI, 15.2%-45.9%) compared with not at all (5.8%; 95% CI, 4.7%-7.2%; adjusted odds ratio [aOR], 8.11; 95% CI, 3.14-20.97). Furthermore, 10.7% (95% CI, 9.1%-12.5%) discontinued daily cigarette smoking, with higher rates of discontinuation observed among those who used e-cigarettes daily (45.5%; 95% CI, 27.4%-64.9%) compared with not at all (9.9%; 95% CI, 8.2%-11.8%; aOR, 9.67; 95% CI, 4.02-23.25). Nondaily e-cigarette use was not associated with cigarette discontinuation (aOR, 0.53; 95% CI, 0.08-3.35) or daily cigarette discontinuation (aOR, 0.96; 95% CI, 0.44-2.09).

Conclusions and Relevance  In this cohort study, daily e-cigarette use was associated with greater odds of cigarette discontinuation among smokers who initially had no plans to ever quit smoking. These findings support the consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.

The full citation is: Kasza KA, Edwards KC, Kimmel HL, et al. Association of e-Cigarette Use With Discontinuation of Cigarette Smoking Among Adult Smokers Who Were Initially Never Planning to Quit. JAMA Netw Open. 2021;4(12):e2140880. doi:10.1001/jamanetworkopen.2021.40880. It is available here.

Published by Stanton Glantz

Stanton Glantz is a retired Professor of Medicine who served on the University of California San Francisco faculty for 45 years. He conducts research on tobacco and cannabis control and cardiovascular disease/

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