title: Electronic cigarettes for smoking cessation and reduction.
abstract: BACKGROUND
  Electronic cigarettes (ECs) are electronic devices that heat a liquid - usually comprising propylene glycol and glycerol, with or without nicotine and flavours, stored in disposable or refillable cartridges or a reservoir - into an aerosol for inhalation. Since ECs appeared on the market in 2006 there has been a steady growth in sales. Smokers report using ECs to reduce risks of smoking, but some healthcare organisations have been reluctant to encourage smokers to switch to ECs, citing lack of evidence of efficacy and safety. Smokers, healthcare providers and regulators are interested to know if these devices can reduce the harms associated with smoking. In particular, healthcare providers have an urgent need to know what advice they should give to smokers enquiring about ECs.
  
  
  OBJECTIVE
  To examine the efficacy of ECs in helping people who smoke to achieve long-term abstinence; to examine the efficacy of ECs in helping people reduce cigarette consumption by at least 50% of baseline levels; and to assess the occurrence of adverse events associated with EC use.
  
  
  METHODS
  We searched the Cochrane Tobacco Addiction Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two other databases for relevant records from 2004 to July 2014, together with reference checking and contact with study authors.
  
  
  METHODS
  We included randomized controlled trials (RCTs) in which current smokers (motivated or unmotivated to quit) were randomized to EC or a control condition, and which measured abstinence rates or changes in cigarette consumption at six months or longer. As the field of EC research is new, we also included cohort follow-up studies with at least six months follow-up. We included randomized cross-over trials and cohort follow-up studies that included at least one week of EC use for assessment of adverse events.
  
  
  METHODS
  One review author extracted data from the included studies and another checked them. Our main outcome measure was abstinence from smoking after at least six months follow-up, and we used the most rigorous definition available (continuous, biochemically validated, longest follow-up). For reduction we used a dichotomous approach (no change/reduction < 50% versus reduction by 50% or more of baseline cigarette consumption). We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for each study, and where appropriate we pooled data from these studies in meta-analyses.
  
  
  RESULTS
  Our search identified almost 600 records, from which we include 29 representing 13 completed studies (two RCTs, 11 cohort). We identified nine ongoing trials. Two RCTs compared EC with placebo (non-nicotine) EC, with a combined sample size of 662 participants. One trial included minimal telephone support and one recruited smokers not intending to quit, and both used early EC models with low nicotine content. We judged the RCTs to be at low risk of bias, but under the GRADE system the overall quality of the evidence for our outcomes was rated 'low' or 'very low' because of imprecision due to the small number of trials. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. Participants using an EC were more likely to have abstained from smoking for at least six months compared with participants using placebo EC (RR 2.29, 95% CI 1.05 to 4.96; placebo 4% versus EC 9%; 2 studies; GRADE: low). The one study that compared EC to nicotine patch found no significant difference in six-month abstinence rates, but the confidence intervals do not rule out a clinically important difference (RR 1.26, 95% CI: 0.68 to 2.34; GRADE: very low). A higher number of people were able to reduce cigarette consumption by at least half with ECs compared with placebo ECs (RR 1.31, 95% CI 1.02 to 1.68, 2 studies; placebo: 27% versus EC: 36%; GRADE: low) and compared with patch (RR 1.41, 95% CI 1.20 to 1.67, 1 study; patch: 44% versus EC: 61%; GRADE: very low). Unlike smoking cessation outcomes, reduction results were not biochemically verified.None of the RCTs or cohort studies reported any serious adverse events (SAEs) that were considered to be plausibly related to EC use. One RCT provided data on the proportion of participants experiencing any adverse events. Although the proportion of participants in the study arms experiencing adverse events was similar, the confidence intervals are wide (ECs vs placebo EC RR 0.97, 95% CI 0.71 to 1.34; ECs vs patch RR 0.99, 95% CI 0.81 to 1.22). The other RCT reported no statistically significant difference in the frequency of AEs at three- or 12-month follow-up between the EC and placebo EC groups, and showed that in all groups the frequency of AEs (with the exception of throat irritation) decreased significantly over time.
  
  
  CONCLUSIONS
  There is evidence from two trials that ECs help smokers to stop smoking long-term compared with placebo ECs. However, the small number of trials, low event rates and wide confidence intervals around the estimates mean that our confidence in the result is rated 'low' by GRADE standards. The lack of difference between the effect of ECs compared with nicotine patches found in one trial is uncertain for similar reasons. ECs appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo ECs and nicotine patches, but the above limitations also affect certainty in this finding. In addition, lack of biochemical assessment of the actual reduction in smoke intake further limits this evidence. No evidence emerged that short-term EC use is associated with health risk.
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, 55 Philpot Street, Whitechapel, London,  E1 2HJ UK. h.j.mcrobbie@qmul.ac.uk.
authors.forename: Hayden
authors.initials: H
authors.lastname: McRobbie
authors.forename: Chris
authors.initials: C
authors.lastname: Bullen
authors.forename: Jamie
authors.initials: J
authors.lastname: Hartmann-Boyce
authors.forename: Peter
authors.initials: P
authors.lastname: Hajek
mesh_terms: D015331:Cohort Studies; D066300:Electronic Nicotine Delivery Systems / Q000009:adverse effects / Q000295:instrumentation; D006801:Humans; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage; D018722:Nicotinic Agonists / Q000008:administration & dosage; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000453:epidemiology; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D061485:Tobacco Use Cessation Devices
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine