February 4, 2019

Stanton A. Glantz, PhD

RCT comparing e-cigs to NRT shows effectiveness in a supervised smoking cessation program: what it does and does not mean

Peter Hajek and colleagues published “A Randomized Trial of E-cigarettes versus Nicotine-Replacement Therapy” in the New England Journal of Medicine.  This is a well-done trial comparing e-cigarettes with nicotine replacement therapy among people enrolled in smoking cessation programs in England.  In addition to being randomized to e-cigs or NRT, people in the study had ar least 4 weeks of counselling.  At one year the cigarette abstinence rate was 18.0% among patients randomized to e-cigs compared to 9.9% randomized to NRT, nearly a doubling of quitting.

The study is thoughtfully designed and cautiously interpreted.  The authors also did a nice set of sensitivity analyses to show that the results are robust to the usual kinds of problems one has in doing a randomized controlled trial.

They conclude that “E-cigarettes were more effective for smoking cessation that nicotine-replacement therapy, when both products were accompanied by behavioural support.”  I agree with that conclusion.

Having said that, it is important to emphasize that this is not a study of e-cigarettes as most people use them, which is as recreational products not as part of a clinically supervised cessation attempt that, most important, includes intensive counselling.   Thus, the results of the Hajek study do not contradict the overall result that, in the general population, smokers who use e-cigarettes are, on average, less likely to quit smoking.

So, my bottom line is that if other well-done randomized controlled trials show that e-cigarettes improve smoking cessation, the manufacturers should submit the evidence to the appropriate authorities (the FDA in the USA) to get e-cigarettes approved as prescription medicines to be administered by physicians or other health professionals as part of supervised cessation efforts that include intensive counselling. 

The reason that I say they should be available by prescription is because of their high abuse potential, as evidenced by the run-away use of them by kids as well as the fact that when used unsupervised in the general population they depress smoking cessation.

In addition to efficacy, the drug approval process needs to assess safety.  Hajek and colleagues reported that after one year 80% of the e-cigarette group were still using e-cigarettes compared to just 9% of the NRT group were continuing to use NRT.  This is of particular concern because of the evidence linking e-cigarette use to heart attacks and chronic obstructive pulmonary disease and is something that warrants serious consideration by regulatory authorities.

The accompanying editorial by Belinda Borrelli and George T. O’Connor also raises several concerns about long-term safety of e-cigarette use and notes that varenicline -- which was not evaluated in the Hajek study -- outperforms NRT.

Here is the abstract:

BACKGROUND:  E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments.

METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms.

RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.

CONCLUSIONS:  E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

The full citation is Hajek P, et al.  A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.  N Engl J Med. 2019 Jan 30. doi: 10.1056/NEJMoa1808779. [Epub ahead of print].   The paper is available here.

Comments

Comment: 

Subject: Re: RCT comparing e-cigs to NRT shows effectiveness in a supervised smoking cessation program: what it does and does not mean [EXTERNAL] [Bulk]

​I'm a bit confused .Did not the NRT group get a 3 m supply of products and ecigs starter pack and 1 bottle ejuice. I wondered if the NRT groups did the 3 months and then stopped nicotine replacement and after 1 y 9.9% still remained abstinent NOT just from tobacco but also nicotine. Whereas, in the ecig goup 80% of thse who stopped smoking continued abstinent from cigarettes but NOT abstinent from nicotine. So if my interpretation is correct and we redefine successful sustained abstinence as including both of cigarettes and nicotine. Then in fact the rate in the NRT group is twice as successful in sustained abstinence as ecigs. Am I missing something here?

Lester J. Hartman, MD MPH FAAP
Westwood-Mansfield Pediatric Associates
781-326-7700 | [email protected] | https://protect2.fireeye.com/url?k=62b75c87-3ef731d1-62b77b9a-0cc47adb57...
"Proactive in your child’s care. Empowering families for over 55 years."
@DrHartmanWMPEDS | #Tobacco21

Comment: 

The Hajek study used intended quit- by- any -means volunteers, removed dual users and tossed a coin (randomized) the remaining volunteers into two groups all of whom were offered the standard UK 12 week NHS counselling with their allocated pharmaceuticals (NRT group) or tank system e-cig. Varenicline or Chantix use with counselling were excluded from the Hajek study.
The study authors did not reveal the brand names of the volunteers’ cigarettes or nicotine yield content as provided in a Canada Intense smoking test report to show realistic smoker intake levels per brand. As the volunteer nicotine intake starting point
The patches supplied in UK are 7, 14 or 21mg and cannot be adjusted by the user.
The tank system group was encouraged to seek out and use e-juice that best suited their flavour choice or nicotine yield requirement.
Flavored e-juice at 36ml nicotine per mL is easily available and accessible online in UK or DIY mixes.

The study authors might have considered a control (NRT group) E-cig choose-- your –own- blend- and- strength group, Varenicline group, JUUL group and another name brand closed pod system e-cig group – all with counselling …. But they didn’t

The timeframe of the Hajek study beyond a couple of phone calls over 9 months leaves many questions of what actually happened in the two groups.

Varenicline with counselling – stunning results at 6 months abstention vs control
https://bmjopen.bmj.com/content/6/1/e009381
Effectiveness of Varenicline and counselling for smoking cessation in an observational cohort study in China

https://www.nejm.org/doi/10.1056/NEJMoa1808779
Hajek et al - A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy

https://www.nejm.org/doi/full/10.1056/NEJMe1816406?query=recirc_curatedR...
Editorial NEJM on above Hajek study
E-Cigarettes to Assist with Smoking Cessation
• Belinda Borrelli, Ph.D.,
• and George T. O’Connor, M.D.

It seems UK academics are unable to find the study by (E-cig supporter) West et al which monitored 200,000 UK e-cig users over a ten year period, and the study outcome
https://bmjopen.bmj.com/content/8/6/e016046
Beard E, et al. BMJ Open 2018;8:e016046. doi:10.1136/bmjopen-2017-016046
Is prevalence of e-cigarette and nicotine replacement therapy use among smokers associated with average cigarette consumption in England? A
time-series analysis

We have yet to find any electronic cigarette product /nicotine e-juice which has been tested and certified by any worldwide Government as a smoking cessation / harm reduction product, yet
the UK especially continues to promote these untried untested paraphernalia with a growing list of pathogenic harms and , explosions.

One of the Hajek study co-authors issued this study: (Dawkins)
http://www.lsbu.ac.uk/about-us/news/ex-smokers-vaping-trial-nicotine-e-cigs
“Results of a new E-cig trial carried out by researchers at LSBU show that vapers using low nicotine e-cigarettes puff harder, for longer and more often, inhaling more cancer-causing chemicals”

Yet the Hajek study shows the E-cig cohort of the study was apparently still 80% addicted to e-cigs and nicotine at one year follow-up, and ergo ’inhaling more cancer causing chemicals”

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