If e-cigs are effective cessation aids, when will an e-cig company submit the needed evidence for FDA approval?

JAMA just published another randomized controlled trial, “Effect of e-cigarettes plus counseling vs counseling one on smoking cessation,” that found that giving smokers who were motivated to quit free NJOY e-cigs for 12 weeks together with intensive counseling led to significantly more quitting at 12 weeks than counseling alone. The effect faded by 24 weeks, with no significant difference between e-cigs with and without counseling.

The study, from Canada, is well done an carefully analyzed and interpreted and consistent with other RCTs that show that e-cigs, as a form of nicotine replacement therapy (NRT), delivered as part of active supervised treatment at least increase cessation in the short term.

To assess the effects of e-cigs as a medicine, the investigators took care to not include any people who were already using e-cigs (or any conventional smoking cessation therapy). Given that these people were e-cigarette naive, however, it is concerning that 37% of the people given nicotine e-cigarettes and 23% given non-nicotine were still using them at 24 weeks (12 weeks after the supply of free e-cigs ended), turning them from smokers into dual users (i.e., using e-cigarettes while continuing to smoke).

This is a serious adverse effect of e-cigarettes for cessation because dual use is associated with higher risk of lung and heart (for example, Alzahrani et al , Osei et al) disease than smoking alone. E-cigarettes also adversely impact blood vessels similar to cigarettes (for example, Rao et al, Fetterman et al). And there is lots more evidence of harm rapidly accumulating.

Moreover, as I have pointed out before, however, the vast majority of e-cigarettes are purchased and consumed as consumer products not medicines that RCTs are designed to assess. This study provides no useful information about the effects of e-cigarettes as consumer products on cessation in the general population, which is a key question the FDA Center for Tobacco Products must address when deciding whether to authorize the sale of e-cigarettes as consume products.

In an accompanying editorial, Nancy Rigotti says that “investigators’ ability to conduct these trials has been slowed by Food and Drug Administration (FDA) requirements.”

This is poppycock. The fact that there are many RCTs of e-cigs for smoking cessation in the literature (including this one) shows that they are not that hard or expensive to conduct. Moreover, the e-cig companies are being required to submit the same kind of information on safety and health effects as part of the Premarket Tobacco Product Applications (PMTAs) they have already submitted to FDA for authorization to continue selling e-cigs as consumer products in the United States.

My guess is that the companies have not submitted applications to FDA to sell and promote e-cigs as cessation therapies for three reasons: (1) They are not all that effective in the long run, (2) even if they pass the “effective” screen, they are likely much more dangerous than current approved therapies, so would not have a favorable benefit/risk ratio, and (3) they would likely be limited to prescription use because of the high addictive potential, which would limit the market.

Indeed, the fact that so many people in the study continued using e-cigs after the study ended supports this concern about an adverse benefit/risk ratio.

In any event, for e-cigarettes to be even considered as a smoking cessation therapy, the time has come for a real e-cigarette company to submit the needed data to the FDA Center for Drug Evaluation and Research (and comparable agencies around the world that approve medicines) making the case that a specific e-cigarette given to a specified group of smokers using a specified protocol is effective and safe as a smoking cessation therapy.

Until that happens, physicians, smoking cessation practitioners and public health professions (and the FDA Center for Tobacco Products) should stop saying or implying that e-cigs help people quit smoking and the FDA Center for Drug Evaluation and Research should clamp down on the illegal cessation claims that are being used to promote e-cigarettes.