November 10, 2020

expert reaction to the randomised control trial on e-cigarettes for quitting smoking

The randomised control trial published in JAMA looks at the effect of e-cigarettes plus counselling vs counselling alone on smoking cessation.

Dr Jamie Hartmann-Boyce, Senior researcher in Health Behaviours and Managing Editor of the Cochrane Tobacco Addiction Group, University of Oxford, said:

“Randomized controlled trials are considered the best way to test if a treatment works. In this study, the researchers randomized people who smoke to nicotine e-cigarettes, e-cigarettes without nicotine, or no e-cigarettes. No participants in the study experienced serious harms from e-cigarettes.

“More people quit smoking with the nicotine e-cigarette than with no e-cigarette at 12 weeks, but at 24 weeks there was less of a difference between groups. The difference between nicotine e-cigarettes and e-cigarettes was not clear.

“As this trial was stopped early, and as not very many participants quit smoking overall, it cannot give a definitive answer. A recent Cochrane review combining results from multiple randomized controlled trials found that e-cigarettes with nicotine can increase the chances of successfully quitting smoking. More studies are still needed in this area, preferably with e-cigarette devices that are representative of what’s on the market at the time, and with longer-term follow-up.”

Prof John Britton, Emeritus Professor of Epidemiology, University of Nottingham, said:

“This study demonstrates that using a nicotine-containing e-cigarette and counselling are approximately twice as likely to quit smoking than smokers receiving counselling alone. This difference was statistically significant at three months and although no longer statistically significant remained of similar relative magnitude at six months.

“The finding is entirely consistent with that of an earlier and larger UK trial (Hajek et al 2019) which, thanks to larger numbers, confirmed a statistically significant effect of similar magnitude at 12 months. The implication of these findings is that e-cigarettes are effective stop-smoking aids.”

Prof Paul Aveyard, Professor of Behavioural Medicine, University of Oxford, said:

“This is a well-conducted study that has one major weakness – it is too small to produce reliable evidence of the effectiveness of e-cigarettes. This is because the study was designed to be too small and then was unable to recruit its target number of people into the study because of problems making the e-cigarettes.

“The primary outcome of the study was abstinence from smoking 12 weeks after attempting to quit smoking. Scientists declare a primary outcome in advance to ensure that this is a fair test of the ability of treatment to achieve a benefit. Doing so aims to minimise the possibility that the play of chance is explaining the findings. On the basis of the primary outcome, this trial shows that e-cigarettes containing nicotine improve the likelihood of stopping smoking but we are unsure whether e-cigarettes without nicotine do so.

“A recent comprehensive analysis of all trials of e-cigarettes found moderately strong evidence that e-cigarettes increase the likelihood of people stopping smoking and these results are likely to strengthen that. However, this trial was the first to give us evidence on the benefits of e-cigarettes that do not contain nicotine and it suggests that these may be modestly beneficial, but the unreliability of the trial means we remain uncertain.

“For anyone looking to stop smoking and considering using an e-cigarette, the best advice remains to use an e-cigarette with e-liquid that contains nicotine.”

Dr Nicola Lindson, Cochrane Tobacco Addiction Group Senior Leader, University of Oxford, said:

“Although the results of this study appear to show that the effects of the e-cigarette reduce over time we need to be very careful about how we interpret the long-term (1 year) findings. There were problems during the study (which the researchers recognise), which meant that the researchers were not able to recruit all of the people that they needed to measure the outcome at 1 year. This means we can be more confident about the findings at 12 weeks than the findings at 1 year. When we look at the range of possible effects at 1 year this suggests that there could be a benefit of e-cigarettes but the number of people taking part means we cannot be confident about this.

“This paper by the authors (https://www.cjcopen.ca/article/S2589-790X(20)30030-5/fulltext) highlights their issues with statistical power and that they changed their primary outcome from 1 year to 12 weeks for this reason.”

Dr Nick Hopkinson, Reader in Respiratory Medicine, Imperial College London, said:

“This study adds to the evidence that providing alternative sources of nicotine to reduce withdrawal effects, in this case through e-cigarettes, can help people to quit smoking successfully.

“The researchers took people who wanted to quit smoking and randomly allocated them to counselling alone or counselling combined with either 12 weeks of nicotine e-cigarettes or non-nicotine e-cigarettes. The results show that that people were more than twice as likely to quit successfully using e-cigarettes at 12 weeks compared to counselling alone (2.4 times more likely, or 21.9%vs 9.1% successful quit rate) which was the primary endpoint of the trial.  Quitting smoking was confirmed by measuring carbon monoxide levels in participants’ breath, so we can be confident that smoking/quitting has been captured accurately.

“By 24 weeks the difference between groups was a little smaller (1.7 times more likely, 17.2%vs 9.9%). This still looks like an important effect, but there were not enough people in the study to confirm that it is statistically significant. The study only recruited 77% of its target number of participants (376 (77%of 486 target sample)).”

Prof Peter Hajek, Director of the Tobacco Dependence Research Unit, Queen Mary University of London (QMUL), said:

“The study followed a protocol that differs markedly from the way smokers use e-cigarettes in real life. Participants were given an early tobacco-flavoured product with low nicotine content, rather than being allowed to select flavours and strengths of their choice; and they had to stop use and return any unused supplies at 12 weeks. Despite this, the differences in 7-day abstinence rates between participants who did and did not receive EC were large, though with the small sample size, some did not reach statistical significance. Continuous abstinence rates, a much more important metric than just not smoking for 7 days, were very low, but about four times higher with vaping (4% vs 1%). The low figures are most likely due to the fact that, unusually for this type of trials and for clinical practice, participants were not given a target quit date.   

“The trial also included nicotine-free e-cigarettes, but the results do not tally with previous studies and participants could not tell which is which (about half guessed they are getting nicotine in both groups). This is baffling, even for a low nicotine delivery product, and raises questions about possible errors in product labelling.”

‘Effect of e-Cigarettes Plus Counseling vs Counseling Alone on Smoking Cessation’ by Mark J. Eisenberg et al. was published in JAMA at 4pm UK time on Tuesday 10 November.

doi:10.1001/jama.2020.18889

Declared interests

Dr Hartmann-Boyce: “No conflicts of interest to declare.”

Prof Aveyard: “No conflicts.”

Prof Hopkinson: “is the Chair of Action on Smoking and Health (ASH) and Medical Director at the British Lung Foundation.”

None others received.