Oxford review: E-cigarettes versus traditional nicotine replacement therapies

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A University of Oxford study has provided greater confidence that e-cigarettes with nicotine can help more people to quit smoking than traditional nicotine replacement therapy (such as gums or patches) or e-cigarettes without nicotine, reports The Conversation.

The Oxford researchers, using standard Cochrane Review methods, examined evidence from the covering 50 studies and more than 12,000 participants.

Electronic cigarettes are a popular aid for quitting smoking. But it is taking time for scientific research to catch up and provide clear answers on how well they work, and whether they are safe to use for this purpose, write Oxford senior researchers Jamie Hartmann-Boyce and Nicola Lindson in The Conversation article published on 14 October 2020.

While the findings are positive for e-cigarettes as an aid to smoking cessation, the evidence is of moderate certainty – and more studies are needed to confirm the degree of effect, particularly testing newer e-cigarette devices.

The review found no evidence of serious harms of e-cigarettes with nicotine. But the data was limited – the longest follow-up was just two years – and considerable uncertainty remains regarding harms.

Better quitting treatments needed

Smoking kills one in two regular users. Most people who smoke want to quit, but quitting smoking can be extremely difficult, and better treatments are needed.

For many, the arrival of e-cigarettes signalled an exciting opportunity. E-cigarettes represented a new treatment for cigarette addiction, mimicking some of the behavioural, social and pharmacological aspects of cigarettes. But some policy-makers remain cautious, despite the increase in research findings that support e-cigarettes for quitting smoking.

Whereas e-cigarettes are widely available in some countries, in other areas current policies include complete bans on e-cigarettes and policies in which e-cigarettes with nicotine are available on prescription only.

Reasons for caution

The caution behind restrictive regulations is not to do with whether people who smoke should switch to e-cigarettes. While there are still unknowns regarding possible longer-term harms of e-cigarettes, experts generally agree that e-cigarettes are considerably less harmful than smoking, even though they are not completely risk free.

Evali, the e-cigarette-related illness that made headlines last year, raised significant concerns around the safety of e-cigarettes. But it was quickly discovered that this was linked to vitamin E acetate – an additive that has been found in unregulated e-cigarette liquids, typically containing THC (the active ingredient in cannabis). This additive is banned from e-cigarettes in many parts of the world, including Europe.

Caution, instead, largely has to do with how the availability of e-cigarettes affects young people. Young people who use e-cigarettes are more likely to go on to smoke.

Some interpret this data to mean that young people who would never smoke experiment with e-cigarettes, become addicted to nicotine and then start smoking. In other words, some argue that e-cigarettes act as a gateway to smoking tobacco.

Others argue that the link is instead due to commonalities between young people who would try e-cigarettes and try smoking regardless – the idea that: “kids who try things, try things”. While research is ongoing on this, debates on policy divide into “help the adults quit” and “protect the kids”.

Not mutually exclusive

Helping adults quit and protecting kids are not mutually exclusive.

Children whose parents smoke are around three times more likely to smoke in later life. Whereas second-hand smoke is known to cause many health problems in infants and children, including sudden infant death syndrome, the harm of e-cigarette vapour to bystanders appears far less than that from cigarettes.

By acknowledging that helping adults quit smoking is also a way to protect kids, it may be possible to move the debate along. This is needed to craft regulations that both prevent young people from starting to use e-cigarettes and from starting to smoke, and help the adults around them to stop smoking.

One approach that has been tried is to reduce the amount of nicotine in e-cigarettes. But studies have shown that this may have unintended effects – people who smoke seem to puff harder on e-cigarettes with a lower nicotine content to get the nicotine levels they seek.

Nicotine is not the chemical that causes the many diseases linked to smoking. In fact, nicotine replacement therapy, which provides nicotine without the other harmful chemicals from cigarettes, has been available to help people safely stop smoking for decades.

Despite its wide availability, there is very little evidence that non-smokers use it. This is down to a combination of factors, but marketing and regulation have undoubtedly played important roles.

Informing policy

The regulation of e-cigarette sales and marketing varies substantially worldwide.

Though this muddies the waters when communicating potential benefits and harms of e-cigarettes, regional differences in e-cigarette use among young people may help guide effective regulation in the future.

For example, researchers and policy-makers can look to areas where e-cigarette use in young people is low and compare regulations to those in place in areas where e-cigarette use in young people is more widespread.

Ideally, lessons could be learned about ways to ensure e-cigarettes are readily available to people struggling to quit smoking, but are not appealing to people who don’t smoke.

The tension between “protecting the kids” and “helping adults who smoke” has been getting in the way of clear public health messaging for years.

As new evidence emerges, the message remains the same: e-cigarettes with nicotine are not risk free but are considerably less harmful than smoking. Translated into actions: if you don’t smoke, don’t start to use e-cigarettes. If you do smoke, consider switching.

* Jamie Hartmann-Boyce is Senior Research Fellow, Departmental Lecturer and Co-Director of Evidence-Based Healthcare DPhil programme, Centre for Evidence-Based Medicine, University of Oxford. Nicola Lindson is Senior Researcher, Nuffield Department of Primary Care Health Sciences, University of Oxford.


Electronic cigarettes for smoking cessation

Cochrane Systematic Review – Intervention Version published on 14 October 2020


Jamie Hartmann-Boyce, Hayden McRobbie, Nicola Lindson, Chris Bullen, Rachna Begh, Annika Theodoulou, Caitlin Notley, Nancy A Rigotti, Tari Turner, Ailsa R Butler and Peter Hajek. The affiliating institution is the University of Oxford.


Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e‐liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. 


To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long‐term smoking abstinence. 

Search methods

We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference‐checking and contact with study authors. 

Selection criteria

We included randomised controlled trials (RCTs) and randomised cross‐over trials in which people who smoke were randomised to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention.

To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. 

Data collection and analysis

We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow‐up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants.

We used a fixed‐effect Mantel‐Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta‐analyses. 

Main results

We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty‐five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non‐randomized studies), and the remainder at unclear risk. 

There was moderate‐certainty evidence, limited by imprecision, that quit rates were higher in people randomised to nicotine EC than in those randomised to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8).

There was low‐certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). 

There was moderate‐certainty evidence, again limited by imprecision, that quit rates were higher in people randomised to nicotine EC than to non‐nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12).

These trials used EC with relatively low nicotine delivery. There was low‐certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants).

Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low‐certainty, due to issues with imprecision and risk of bias.

There was no evidence that the rate of SAEs varied, but some evidence that non‐serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). 

Data from non‐randomised studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. 

Authors' conclusions

There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain.

More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers.

Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow‐up was two years and the overall number of studies was small. 

The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway.

To ensure the review continues to provide up‐to‐date information for decision‐makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.


New evidence shows e-cigarettes can help people quit smoking


Electronic cigarettes for smoking cessation


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