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HomeHarm ReductionJAMA editorial: Research strengthens case for e-cigarettes for smoking cessation

JAMA editorial: Research strengthens case for e-cigarettes for smoking cessation

Research shows that electronic cigarettes can help smokers to quit smoking cigarettes, according to an editorial in JAMA by Dr Nancy Rigotti, director of the Tobacco Research and Treatment Center at Massachusetts General Hospital and a professor of medicine at Harvard Medical School.

Nearly a half million Americans die each year from tobacco-related diseases such as lung cancer, heart attacks, strokes and emphysema, which makes smoking the leading preventable cause of death in the United States, Massachusetts General Hospital reports.

Most smokers want to stop, and more than half try to quit each year, but only 5% to 7% are able to abstain long term. Using treatments approved by the Food and Drug Administration (FDA) increases the likelihood of success, but many smokers who use these therapies still struggle to remain tobacco free, says Rigotti.

She sees a promising role for e-cigarettes as a new option to help smokers quit. E-cigarettes are handheld devices filled with a liquid that usually contains nicotine and flavourings. The device heats the liquid to produce an aerosol that's inhaled, or ‘vaped’.

The devices appeal to smokers trying to quit because they mimic the experience of smoking while providing nicotine to avoid withdrawal symptoms.

Since e-cigarettes don't burn tobacco, users don't inhale toxin-filled smoke, as with conventional cigarettes. While not harmless, using e-cigarettes is likely far less dangerous than continuing to smoke conventional cigarettes.

Sceptics note that e-cigarettes are not approved medicine for smoking cessation. Rigotti counters that there's an urgent need for evidence showing that e-cigarettes are safe and effective at helping smokers quit.

In October, Rigotti and several colleagues published a review of 50 studies, which included 12,430 adult smokers, that evaluated e-cigarettes as smoking-cessation aids in the prestigious Cochrane Database of Systematic Reviews.

Overall, Rigotti and her co-authors found increasing evidence that e-cigarettes containing nicotine are more effective at helping smokers quit for at least six months than nicotine-replacement therapy (such as skin patches and chewing gum), nicotine-free e-cigarettes and behavioural counseling.

Rigotti's editorial appears in an issue of JAMA that also features a new study of e-cigarettes, which found that abstinence from smoking after three months was higher among participants using the devices than those who only received counselling.

"We need more randomised trials because there is still a lot we don't know," says Rigotti. In particular, she calls for studies of new-generation ‘pod-type’ e-cigarettes (the JUUL brand is one example), which deliver nicotine faster and in higher doses than the older devices studied in the JAMA article.

She also calls for comparing e-cigarettes with other FDA-approved smoking cessation medications and for more research on the health effects of long-term use of e-cigarettes.

For now, FDA-approved therapies should be the first choice for patients who need to stop smoking, says Rigotti. "But what do you say to a smoker who has tried those treatments and failed? Or who isn't willing to try them?"

In that case, Rigotti believes it's reasonable to discuss the potential benefits and harms of e-cigarettes with the patient. "In the debate about e-cigarettes," she says, "we need to remember that there are millions of smokers who need help and could benefit."


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


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 randomized controlled trials (RCTs) and randomized cross‐over trials in which people who smoke were randomized 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 randomized to nicotine EC than in those randomized 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 randomized 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‐randomized 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.


Plain English summary

Can electronic cigarettes help people stop smoking, and do they have any unwanted effects when used for this purpose?

Why we did this Cochrane Review

Stopping smoking lowers your risk of getting lung cancer and other diseases. But many people find it difficult to quit. We wanted to find out if using e‐cigarettes could help people to stop smoking, and if people using them for this purpose experienced any unwanted effects.

What did we do?

We searched for studies that looked at the use of e‐cigarettes to help people stop smoking.

We looked for randomized controlled trials, in which the treatments people received were decided at random. This type of study usually gives the most reliable evidence about the effects of a treatment. We also looked for studies in which everyone received an e‐cigarette treatment.

We were interested in finding out:

  • How many people stopped smoking for at least six months.
  • How many people had any unwanted effects.

We included studies that reported on smoking habits for at least six months, or reported on unwanted effects for at least one week.

Search date: We included evidence published up to January 2020.

What we found

We found 50 studies in 12,430 adults who smoked. The studies compared e‑cigarettes with:

  • Nicotine replacement therapy, such as patches or gum;
  • Varenicline;
  • Nicotine‐free e‐cigarettes;
  • Behavioural support, such as advice or counselling; or
  • No support, for stopping smoking.

Some studies also tested using NRT and e‐cigarettes together.

The studies took place in the USA (21 studies), the UK (9), Italy (7), Australia (2), New Zealand (2), Greece (2), and one study each in Belgium, Canada, Poland, South Korea, South Africa, Switzerland and Turkey.

What are the results of our review?

More people probably stop smoking for at least six months using nicotine e‐cigarettes than using nicotine replacement therapy (3 studies; 1498 people), or nicotine‐free e‑cigarettes (3 studies; 802 people).

Nicotine e‐cigarettes may help more people to stop smoking than no support or behavioural support only (4 studies; 2312 people).

For every 100 people using nicotine e‐cigarettes to stop smoking, 10 might successfully stop, compared with only six of 100 people using nicotine‐replacement therapy or nicotine‐free e‐cigarettes, or four of 100 people having no support or behavioural support only.

We are uncertain if there is a difference between how many unwanted effects occur using nicotine e‐cigarettes compared with using nicotine‐free e‐cigarettes, nicotine replacement therapy, no support or behavioural support only. Similar low numbers of unwanted effects, including serious unwanted effects, were reported for all groups.

The unwanted effects reported most often with nicotine e‐cigarettes were throat or mouth irritation, headache, cough and feeling sick. These effects reduced over time as people continued using nicotine e‐cigarettes.

How reliable are these results?

Our results are based on a small number of studies, and in some the measured data varied widely.

We are moderately confident that nicotine e‐cigarettes help more people to stop smoking than nicotine replacement therapy or nicotine‐free e‐cigarettes. However, these results might change if further evidence becomes available.

We are less confident about how nicotine e‐cigarettes compare with no support, or behavioural support, to stop smoking.

Our results for the unwanted effects are likely to change when more evidence becomes available.

Key messages

Nicotine e‐cigarettes probably do help people to stop smoking for at least six months. They probably work better than nicotine replacement therapy and nicotine‑free e‐cigarettes.

They may work better than no support, or behavioural support alone, and they may not be associated with serious unwanted effects.

However, we need more, reliable evidence to be confident about the effects of e‐cigarettes, particularly the effects of newer types of e‐cigarettes that have better nicotine delivery.

Authors' conclusions 

Evidence suggesting nicotine EC can aid in smoking cessation is consistent across several comparisons. There was moderate‐certainty evidence, limited by imprecision, that EC with nicotine increased quit rates at six months or longer compared to non‐nicotine EC and compared to NRT. There was very low‐certainty evidence (limited by risk of bias as well as imprecision) that EC with nicotine increased quit rates compared to behavioural support alone or to no support.

The effect of nicotine EC when added to NRT was unclear.

None of the included studies (short‐ to mid‐term, up to two years) detected serious adverse events considered possibly related to EC use. The most commonly‐reported adverse effects were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time. In some studies, reductions in biomarkers were observed in people who smoked who switched to vaping, consistent with reductions seen in smoking cessation.


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New research strengthens the case for e-cigarettes as smoking cessation aids


Electronic cigarettes for smoking cessation




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