New Systematic Review Misinterprets E-Cig Evidence to Support Tobacco-Like Restrictions

When systematic reviews are conducted well, they provide a synthesis of the evidence to date as well as an indication of the merits and drawbacks of the studies conducted. However, when the scientific credibility of the analysis can be reasonably called into question the entire review starts to look more like an ill-informed opinion piece than a genuinely objective analysis. This is the case with a new systematic review on e-cigarettes, which after tracing a predictable but still occasionally jaw-droppingly misinformed path through the evidence to date, suggests that e-cigs should be banned in all public places and subject to tobacco-like marketing restrictions.


Bad science seems to go hand in hand with the Center for Tobacco Control Research and Education at the University of California, San Francisco, and it’ll come as no surprise to many that the latest systematic review (referred to as an “unscientific hatchet job” by Dr. Michael Siegel) comes from Rachel Grana, Neal Benowitz and, of course, Stanton Glantz. If you’re looking a good reason to repeatedly bang your head against your desk, you can give it a read for free, but here’s a general summary of what is contained within.




  • If you’re looking for actual reliable information on the state of research into e-cig safety, Dr. Farsalinos and Prof. Polosa’s review is also available for free and worth reading.


  • The new review investigates the safety of e-cigarettes in a horribly one-sided fashion. For example, it pays more attention to a single toxicity study conducted on the un-vaporized liquid over ones conducted on the vapor because it produced a more potentially damaging effect that way.


  • Looking at the effectiveness of electronic cigarettes for quitting smoking, the systematic review focuses heavily on research that was by design incapable of determining the effectiveness of e-cigs for smoking cessation. In some studies, large proportions of participants weren’t even using e-cigs in their quit attempts.


  • The positive results from clinical trials are brushed aside entirely due to minor issues, and the researchers conclude that e-cigarettes are actually detrimental to quitting smoking. This view is not supported by evidence or even basic logic.


  • The researchers suggest that physicians only begrudgingly accept patients wanting to quit smoking through vaping if all else fails, but to still shroud their acceptance in fear-inducing statements such as e-cigarettes “contain toxic chemicals.”


  • Regulators should close their eyes, ignore all evidence of the huge harm reduction potential for electronic cigarettes and proceed to enact sweeping bans on their use in public places, advertising, any e-liquid flavorings, and any health or cessation claims made without sufficient supporting evidence to win over regulators.


The New Review vs. Another Recent Review


Dr. Konstantinos Farsalinos and Prof. Riccardo Polosa also conducted a review of the evidence on e-cigs to date (you can read the summary here), and despite the fact that they were only published around three months apart, the conclusion drawn in this new review appears to be the polar opposite of that in the older one. Could it be that there was a dramatic, consensus-overturning result in the intervening time period between the previous and recent reviews being compiled? Or – as hard as this may be to believe – do Rachel Grana, Neal Benowitz and Stanton Glantz perhaps have some reason to not be presenting an accurate picture of the evidence? We’re unaware of any shocking results warranting such a shift in opinion, so given that the other review is also available for free (after a quick sign-up), if you’re actually looking for a fair analysis of the issue, you can easily read both and form your own viewpoint on who is attempting to distort the evidence.


However, it’ll soon become clear that the ability to spread news stories such as this one is the main purpose of the new study, as well as potentially providing justifications for harsh actions for policy-makers. “Hatchet job” really does sum it up.


The Safety of E-Cigarettes


Safety of electronic cigarettes


The discussion of the safety of e-cigs in the new paper is simultaneously amusing and infuriating. This is largely because coming to the conclusion the authors obviously want to, that e-cigarettes are some huge potential risk and not merely an effective harm reduction tool, isn’t easy since the vast majority of the evidence points in a different direction. The solution used by the authors is to mention the evidence suggesting e-cigs are safe (because to ignore it entirely would be a touch too obvious), but simply to offer no consideration of the broader implications unless the result from the research is in line with their anti-vaping agenda. A perfect example of the approach comes from their treatment of the toxicological research conducted to date.


They reference three cytotoxicity studies, one from Bahl et. al., one from Romagna et. al. and one from Farsalinos et. al.. You may expect these studies to be given equal weight in the analysis, but there is one problem that means that may not be equally valid: the Bahl study tested the liquid itself rather than the vapor (technically an aerosol) produced from it, which is obviously irrelevant to real e-cig use. The solution for the systematic reviewers wasn’t to mention but ultimately discount these invalid findings; in fact, they were arguably given precedence over the more relevant studies, given that almost equal word counts were used to discuss the Bahl findings as were to discuss both of the others combined.


In addition to explaining the findings, they suggest that because stem cells were found to be more sensitive to the liquid than adult lungs, adult lungs aren’t the best way to evaluate the effects of e-cig exposure, and go on to allege that these findings warrant concern for pregnant women who vape or are exposed to second-hand vapor. No such speculation or analysis is offered for the two more representative studies, and this is likely because discussion of these finding would undermine the core message they’re trying to get across.


effects-of-vaping-on-lungsThe same basic pattern is followed throughout the section (and the paper as a whole), with a good example being a study into the effects of vaping on the lungs, which found some increases in airway resistance after vaping. The reviewers point out many of the serious problems with the study but still conclude based on it that “this study suggests that e-cigarette use constricts peripheral airways, possibly as a result of the irritant effects of propylene glycol, which could be of particular concern in people with chronic lung disease such as asthma, emphysema, or chronic bronchitis.” Of course, the researchers actually found no impact on acute lung function in the study, only statistical findings which, as the original authors themselves said “may be too small to be of major clinical importance.”


More outrageously, the group also points the finger at propylene glycol in general, citing a Dow Chemical fact sheet stating that inhalation exposure to glycol mists should be avoided. They don’t mention actual studies, of course, although research in monkeys and rats does exist which suggests that inhaling glycol vapor is actually quite harmless, or the lack of side effects in clinical research to date.


Effectiveness of E-Cigarettes for Quitting Smoking




This area of the paper is much more laughable, because the viewpoint the authors want to propose is only supported by research that didn’t look at the success rates of smokers trying to quit through vaping. Dr. Siegel analyzes the issues with the cited studies in his blog post, in which the researchers generally didn’t even know if the smokers in the “e-cig” group were even using them to try to quit. In fact, in the couple that asked this important question, a substantial portion of the participants classed as e-cig users weren’t using e-cigs to try to quit at all. In one of the studies, 28 percent of the e-cig group didn’t vape in their quit attempt, and in another only 8 percent of the e-cig group were actually trying to quit with e-cigs in the next 30 days.


Their coverage of the clinical research into e-cigs’ effectiveness for quitting is in line with their coverage of positive safety-orientated studies. Three of the four identified trials were discounted by the authors because of a lack of a control group, despite offering initial but positive findings for reduction and cessation of smoking in ordinary smokers and schizophrenia-sufferers who smoke. The final finding, the clinical trial comparing e-cigs to patches, which found that e-cigs were at least as effective as patches after 6 months, was also covered, and couldn’t be so easily pushed aside due to a lack of a control group.


They did cover many of the positive elements of the trial, pointing out that 57 percent of users randomly assigned to nicotine-containing e-cigs at least reduced their cigarette consumption by 50 percent, compared to only 41 percent of those assigned to patches. Additionally, they point out that 78 percent of the nicotine e-cig group adhered to the treatment protocol, compared with only 46 percent of the patch group. Overall, after 6 months, 7.3 percent of the nicotine e-cig group, 5.8 percent of the patches group and 4.1 percent of the no nicotine e-cig group had quit smoking entirely.


For the authors, the findings of this study are worthy of being wholly discounted because the patch users had to go to the pharmacy to get their patches (although they were given vouchers to cover the cost – which is ordinary practice for quit-line callers in New Zealand), which they argue “may have introduced bias against NRT” because the e-cigarettes group’s equipment was posted directly to them. Of course, the greater adherence to the treatment schedule among the e-cig groups could be a sign of this, or alternatively, it could mean that electronic cigarettes are just more enjoyable than nicotine patches, so people were more likely to stick with them. Compare the number of e-cig user forums and discussion groups to those for NRT and the conclusion will be unavoidable: people enjoy vaping a hell of a lot more, and that’s probably why more stuck to the suggested treatment in that group.


The conclusion from the authors is the logic-defying, “Neither Capponnetto et al nor Bullen et al found effects of e-cigarette use on quitting beyond what is seen in unassisted or low-assistance studies of smokers using NRT to quit. In determining the effectiveness of smoking cessation therapy, active drug is considered efficacious when it outperforms placebo; therefore, the evidence to date from clinical trials does not demonstrate that e-cigarettes are efficacious for cessation.”


nicotine-patches-e-cigsThis idiotic statement is based on their utter inability to admit that the e-cig vs. patches trial in particular is sufficient evidence that e-cigs are more effective than a placebo. Patches are approved medicines, which are considered efficacious despite having relatively low quit rates overall, so by the authors’ own definition they must outperform placebos. So, if nicotine e-cigs are as effective as patches and outperform non-nicotine electronic cigarettes, surely they must also be considered to outperform a placebo too? Either they would have to come out and denounce nicotine patches as ineffective, or their position on e-cigs is inconsistent and idiotic. It’s all the more ridiculous because in the paper they acknowledge that newer e-cigs are more effective and likely safer than the cig-a-likes used in the trial, so it’s also fair to expect better quit rates. But that doesn’t stop them from concluding the opposite.


Things then get even stupider. The researchers are really concerned about dual use of e-cigarettes and cigarettes, which as they already pointed out is ordinarily accompanied by a significant reduction in smoking and sometimes even quitting entirely, and believe that the prevalence of dual use means e-cigarettes may increase harm overall. Why? They offer evidence that the benefits of quitting entirely are much greater than those from reducing smoking (which is obvious), then say that dual users (most vapers) will continue smoking for longer than they would have done otherwise, and therefore that e-cigarettes will not reduce overall harm at all. This is only a good argument if you live in a magical fantasy world in which people can just quit smoking altogether with no difficulty or relapses, and one in which the dual users of electronic cigarettes would have also magically quit smoking if e-cigarettes never existed. For now, we should probably base our opinions on reality rather than some fantastical utopia that exists only in our minds.


Policy Recommendations and Advice for Doctors




Having laid out what they clearly see as a compelling case against e-cigs, the researchers also see themselves as sufficiently qualified to give recommendations to lawmakers and physicians regarding electronic cigarettes.


For doctors, the advice is that they should push the approved methods first, but since any attempt to quit should be supported, if patients are unsuccessful or don’t like traditional methods (Chantix and buproprion are suggested as ideal approaches), then the researchers say it’s reasonable to support the patient in quitting through vaping. doctor-e-cigaretteThis is then followed by, “However, subjects should be informed that, although e-cigarette aerosol is likely to be much less toxic than cigarette smoking, the products are unregulated, contain toxic chemicals, and have not been proven as cessation devices.” This would inevitably confuse the issue and provides nothing more than unsupported and illogical fears. If you were a patient hearing that from your doctor, after having failed using existing methods of quitting, would you really be that encouraged to try vaping? Probably not, and since most other approaches had failed for you it’s likely to simply result in continued smoking.


For policy-makers, the basic approach favored by Glantz and colleagues is to treat electronic cigarettes like cigarettes, despite all the evidence thus far indicating that they are vastly less harmful. Specific suggestions include banning indoor vaping, restricting advertising just like cigarette advertising, banning characterizing flavors, prohibiting claims of effectiveness for quitting and prohibiting any health claims unless approved by regulators.


Conclusion – There’s More Where That Came From


This look at some of the more outrageous statements has barely scratched the surface of the seething mass of misleading and idiotic comments in this review. If nothing else, it provides a unique window into how those furiously opposed to vaping see – or want others to see – the evidence on e-cigarettes to date. It hits all the classic points, stoking the fire of the gateway to smoking, “think-of-the-children” argument, mentioning explosions, drug use with e-cigarettes, the notion that e-cigs will somehow prevent people from quitting, assuming that e-cigarettes are all owned by tobacco companies, presenting “straw man” versions of pro-e-cig arguments (using “it’s just water vapor” as a “typical” manufacturer and user claim) and on and on and on…


Hopefully the trend of even anti-smoking groups flat-out refuting claims made by Glantz continues, but I have a sinking, depressing feeling that this will be cited in a serious context terrifyingly soon. It might even be the sort of thing the FDA is looking to jump all over as justification for their industry-decimating regulations.