Vaping as a gateway to smoking – evidence briefing

Annex – Analysis of the existing evidence

Studies concluding that vaping may act as a gateway to smoking

There is agreement in the majority of the reviews examined for this briefing (five out of eight) that vaping may act as a gateway to smoking, despite the limitations of the available studies and a need for more research:

• The National Centre for Epidemiology and Population Health conducted a systematic review of global evidence for the Australian Department of Health which was published in 2022. This concluded that:
  • there is strong evidence from 17 observational studies that never smokers who use e-cigarettes are on average around three times as likely than those who do not use e-cigarettes to initiate cigarette smoking (aOR^[1]: 3.19; 95% CI 2.44 – 4.16); and
  • there is strong evidence from 8 observational studies that non-smokers who use e-cigarettes are around three times as likely as those who do not use e-cigarettes to become current cigarette smokers (aOR: 3.14; 95% CI 1.93 – 5.11; I²=91%^[2]).

While the studies examined in the review consistently observed an increased risk of smoking uptake with e-cigarette use, the magnitude of the risk varied substantially by study.

• The Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) review for the European Commission, published in 2021, concluded that there is moderate evidence that e-cigarettes are a gateway to smoking for young people.

The reviewers highlighted a number of limitations in the studies examined:

• heterogeneity in terms of study design and methodology, sample size, age groups, measurements of experimental use and follow ups;
• geography of the studies, as they were mostly conducted in the US and other non-European Union countries, meaning different regulatory environment, population perspectives on vaping products and prevalence of smoking/vaping, which could impact the association between use of vaping products and subsequent use of tobacco products;
• type of vaping products on the market at the time of the studies, as these did not contain nicotine salts (which may pose a higher likelihood of developing addiction to nicotine as they increase its smoothness and reduce its bitterness).
• An Irish systematic review and meta-analysis, conducted by the Health Research Board and the Health Intelligence Unit and published in 2021, concluded that e-cigarette use was associated with commencement of tobacco cigarette smoking among teenagers in Europe and North America. In particular, the authors found:
  • 4 times higher odds of commencing tobacco cigarette smoking for teenagers who had ever used e-cigarettes at baseline (the odds ratio was marginally lower when only the studies rated as high-quality included in the review were analysed); and
  • a significant two-fold positive association between past-30-day e-cigarette use at baseline and subsequent cigarette smoking initiation at follow-up.

Despite some limitations identified in the studies (e.g. absence of biochemical verification of outcomes and measurements of experimental use), the authors declared moderate confidence that the true effect was probably close to the estimated effect for initiating smoking at follow-up for those who had ever used e-cigarettes at baseline.

• The National Academies of Sciences, Engineering and Medicine (NASEM) published a report on the Public Health Consequences of E-cigarettes in 2018. Regarding the gateway effect, this concluded that there is substantial evidence to suggest e-cigarette use increases the risk of ever using combustible tobacco cigarettes among youth and young adults.

The Committee’s confidence in a possible causal link was based on the consistency of results across studies despite their heterogeneity (e.g. differences in research methods, length of follow up, definitions, locations, etc.).

While noting that ecological trends in e-cigarette use and smoking prevalence in youth didn’t support this causality, and even suggested that vaping was associated with reduced smoking, the Committee highlighted how:

• the rate of reduction of smoking in US youth recorded in previous years had remained consistent since e-cigarettes became popular; and
• that changes in prevalence from 2015 to 2016 among US high school students declined substantially for e-cigarettes but only marginally for combustible tobacco cigarettes.
• The Australia’s national science agency, Commonwealth Scientific and Industrial Research Organisation (CSIRO) published a review on e-cigarettes, smoking and health in 2018. This concluded that there is evidence for a strong positive relationship between use of e-cigarettes and later cigarette smoking among youth, with consistent results in observational studies across different countries.

The use of e-cigarettes with higher concentrations of nicotine was observed to have a stronger association to later conventional cigarette use, although a positive association was found even when non-nicotine e-cigarettes were considered.

The authors identified a number of limitations in the studies examined, such as variations in measurements of use and follow up periods, small sample sizes, lack of data on retention rates and of adjustments for key confounders.

Studies concluding that it is impossible to establish causality between vaping and subsequent smoking

Three reviews out of eight concluded that, although there is a strong association between vaping and subsequent smoking, it is impossible to establish causality and determine whether this is due to a gateway effect:

• A systematic review and meta-analysis conducted by scholars at the University of Bristol, published in 2020, concluded that there was a strong association in observational studies between e-cigarette use among young non-smokers (up to the age of 30) and subsequent cigarette smoking.

Results indicated e-cigarette users had four-and-a-half-fold higher odds of subsequently reporting being smokers compared to those who never used e-cigarettes. The pooled adjusted estimate indicated a weaker but still strong association (three-fold increased odds). The association was stronger in:

• studies including those under the age of 18 years than studies excluding them, suggesting that decision making for health-risk behaviours is influenced by peers, societal influences and parental monitoring; and
• studies based in the UK compared to those based in the US, possibly due to factors such as legislation, taxation, social norms and public opinions.

While estimates were consistently in the same direction of indicating a plausible causal pathway, the evidence was limited by the reliance on self-report measures of smoking history without biochemical verification, lack in all studies of negative controls (which would support the causality hypothesis) and failure in most studies to consider the nicotine content of e-liquids (making it impossible to establish whether addiction was the driving mechanism determining tobacco smoking). Hence, the authors concluded that the results do not provide strong evidence of a gateway effect.

• A systematic review and meta-analysis, conducted by scholars at the University of Queensland (Australia) and published in 2020, concluded that there is a significant longitudinal association between adolescent vaping and smoking initiation. According to the authors’ meta-analysis, those who initiated vaping during adolescence had a 2.93 times higher odds of future smoking initiation.

However, the authors highlighted that the current evidence is limited by publication bias, high sample attrition and inadequate adjustment for potential confounders, and argued that pooled estimates from the examined studies are likely to overestimate the true effect of vaping on later smoking.

Given these limitations, the review concluded that it is unclear whether the relationship between vaping and subsequent smoking is causal (gateway effect) or is due to common liability (a propensity to substance use that could explain the combined risk of becoming both vaper and smoker).

• The Public Health England evidence review on e-cigarettes and heated tobacco products, published in 2018, concluded that in the UK never smokers who had tried e-cigarettes were more likely to try smoking subsequently than those who had never tried e-cigarettes.

Highlighted limitations in the studies examined by the reviewers pertained to measurements of use and impossibility to control for all relevant confounders. Given the impossibility to establish a causal link, the reviewers considered the common liability hypothesis as a more plausible explanation of the relationship between vaping and subsequent smoking.