The prospective association between smoking and electronic cigarette use in a cohort of young people in Great Britain Katherine East, Sara C Hitchman, Ioannis Bakolis, Sarah Williams, Hazel Cheeseman, Deborah Arnott, Ann McNeill This is part of my PhD.

Conflicts of interest In collaboration with Funded by , and here are my potential conflicts of interest.

Background Baseline Follow-up Young people Baseline Follow-up E-cigarette use Smoking initiation Soneji et al. (2017), US meta-analysis OR=3.62, 95% CI, 2.42-5.41 Best et al. (2017), Scotland OR=2.42, 95% CI=1.63-3.60 Conner et al. (2017), England OR=4.06, 95% CI=2.94-5.60 E-cigarette use Smoking There have been several recent studies finding that young people who have ever used an e-cigarette are more likely to initiate smoking later. PAUSE. However, Leventhal and colleagues found evidence that this association might work both ways among young people in the US. Given the policy implications of these potential associations, it is vital to broaden evidence across countries. Leventhal et al. (2015), US: Ever EC  smoking initiation OR=1.75, 95% CI=1.10-2.77 Ever smoking  EC initiation OR=1.88, 95% CI=1.28-2.76

Four Aims To explore, among young people (11-18y) in GB: Baseline Follow-up Ever EC use Smoking initiation Baseline never smokers Following on from Leventhal, our study has four main aims. The first is to see whether ever e-cigarette use is associated with smoking, and our second is to explore this the other way around. Ever smoking EC initiation Baseline never e-cigarette users

Four Aims To explore, among young people (11-18y) in GB: Baseline EC escalation Baseline Follow-up Ever EC use Smoking initiation Baseline never smokers Our third and fourth aims are to see whether escalation of either product contributes to initiation of the alternative product. PAUSE So, how did we do this? Smoking escalation Ever smoking EC initiation Baseline never e-cigarette users

Method: Design and Sample 2016 Action on Smoking and Health (ASH) GB youth longitudinal survey Age 11-18 Baseline: April 2016; Follow-up: August-October 2016 Ipsos MORI online panels Quota sampling – age, gender, region 1,152 in final sample (from 2,916 at baseline, 50% lost to follow-up, 11% excluded) 20% smokers, 11% e-cigarette users PAUSE

Initiation = never (baseline)  ever (follow-up) Method: Measures Smoking = ever (even a puff) vs. never smoked E-cigarette use = ever (even a puff) vs. never use Escalation = increased between baseline and follow-up (includes initiators) Initiation = never (baseline)  ever (follow-up) PAUSE

Method: Covariates Age Gender School performance Problem behavior Alcohol use Susceptibility to smoking, e-cigarettes Some friends smoke, use e-cigarettes Parents smoke, use e-cigarettes Siblings smoke, use e-cigarettes Public approve of smoking, e-cigarettes We also explored the possible influence of shared risk factors, and therefore included the following covariates PAUSE

Method: Analyses Unadjusted and adjusted logistic regression analyses: 1. Baseline never smokers (n=923): EC use + escalation + covariates  smoking initiation 2. Baseline never EC (n=1,020): Smoking + escalation + covariates  EC initiation Weighted at W2 (age, gender, region) and for attrition (age, gender, region, ever smoking, ever e-cigarette) PAUSE

Baseline Follow-up EC escalation Smoking initiation EC use Numbers of never smokers who had used an e-cigarette very small. PAUSE Baseline never smokers (n=923)

Baseline Follow-up Smoking escalation EC initiation Ever smoking Numbers of never e-cigarette users who had smoked much larger. PAUSE Baseline never e-cigarette users (n=1,020)

Covariates Smoking only first Then EC Then friends both PAUSE

Discussion AND Baseline Follow-up EC escalation Smoking initiation EC use Smoking initiation AND Our results confirm the strong AND consistent association between e-cigarette use and smoking initiation. Our results further suggest that this might work both ways. PAUSE Furthermore, the finding that escalation of each product contributes to initiation of the alternative product is novel, and suggests that for some young people use of both products may occur over a short time frame (4-6 months), and no previous studies have yet explored this possibility. Smoking escalation Smoking EC initiation

Limitations and strengths Observational survey data, likely additional confounders Attrition high and some groups not well represented: ever smokers, ever e-cigarette users, males, older, poor school performance, greater problem behaviour Small sample size, used “ever use”, criticised for limited real-world significance Strengths Novel in accounting for escalation between waves Data from population of GB, quota sampling and weighting However, our findings must be considered in light of some limitations. PAUSE Although this study controlled for a variety of factors, there are still several factors that were not included that may contribute to the observed association between these products, such as genetic factors. Attrition was high and there was evidence that, compared with respondents retained, those lost to follow-up were more likely to have ever smoked and ever used an e-cigarette, and also differed on a number of covariates. Another important limitation is that this study uses the outcomes smoking initiation and e-cigarette initiation defined as progressing from never to ever use of each product. This is similar to some previous studies [12-16], yet the use of such broad measures has been criticised for providing limited evidence of progression to any significant smoking behaviour [21, 27]. However due to the low prevalence rates of monthly or more smoking (5%) and e-cigarette use (2%) in this study’s sample, options for refining the measures were limited. Therefore, although the present study found an association between ever use of smoking and ever use of e-cigarettes, these cannot be generalised to current or regular use. Surveys with multiple waves across several years with larger sample sizes are needed to enable higher numbers of ever and current smokers and e-cigarette users and further dissect the association between the two products. A novel statistical approach (causal mediation analysis [24]) was used to explore whether the association between baseline ever e-cigarette use and smoking initiation at follow-up was mediated by use of e-cigarettes between survey waves; the same procedure was also used to explore further the association between smoking and e-cigarette initiation. To our knowledge this has not been done previously. Finally, the sample was drawn from the general population in Great Britain using a quota sampling approach to enhance representativeness.

Implications Evidence for a two-way relationship between e-cigarette use and smoking in GB young people Need studies with more smokers and e-cigarette users and multiple waves – dynamics Cannot imply causation Possible explanations Common liability model (Van Leeuwen et al., 2011; Vanyukov et al.,2012): experimentation with both products Our findings suggest that there may be a two-way relationship between e-cigarettes and smoking, and it’s not always necessarily that e-cigarette use leads to smoking as suggested by some articles and the media. In order to explore these associations further, we need studies with greater numbers of smokers and e-cigarette users with multiple ways to explore the dynamics further e.g. cross-lagged model. PAUSE As our data were drawn from a survey, we cannot imply causation or say exactly why we have observed these patterns in the general GB population. However, some researchers have suggested that there may be potential common liabilities pertaining to use of both products, or that individuals who are going to try one product are likely to try another. More research is needed in this area to better understa

Questions? The prospective association between smoking and electronic cigarette use in a cohort of young people in Great Britain Katherine East, Sara C Hitchman, Ioannis Bakolis, Sarah Williams, Hazel Cheeseman, Deborah Arnott, Ann McNeill

References Best, C., Haseen, F., Currie, D., Ozakinci, G., MacKintosh, A. M., Stead, M., Eadie, D., MacGregor, A., Pearce, J., Amos, A., & Frank, J. (2017). Relationship between trying an electronic cigarette and subsequent cigarette experimentation in Scottish adolescents: a cohort study. Tobacco Control, tobaccocontrol-2017. Conner, M., Grogan, S., Simms-Ellis, R., Flett, K., Sykes-Muskett, B., Cowap, L., Lawton, R., Armitage, C. J., Meads, D., Torgerson, C., West, R., Siddiqi, K. Do electronic cigarettes increase cigarette smoking in UK adolescents? Evidence from a 12-month prospective study. Tobacco Control Published Online First: 17 August 2017. doi: 10.1136/tobaccocontrol-2016-053539 Leventhal AM, Strong DR, Kirkpatrick MG, et al. Association of electronic cigarette use with initiation of combustible tobacco product smoking in early adolescence. JAMA 2015;314(7):700-707. DOI: 10.1001/jama.2015.8950. Soneji, S., Barrington-Trimis, J. L., Wills, T. A., Leventhal, A. M., Unger, J. B., Gibson, L. A., Yang, J., Primack, B.A., Andrews, J.A., Miech, R.A. & Spindle, T. R. (2017). Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults: A systematic review and meta-analysis. Jama Pediatrics, 171(8), 788-797. Van Leeuwen AP, Verhulst FC, Reijneveld SA, et al. Can the gateway hypothesis, the common liability model and/or, the route of administration model predict initiation of cannabis use during adolescence? A survival analysisthe TRAILS study. J Adolesc Health 2011;48(1):73-78. Vanyukov MM, Tarter RE, Kirillova GP, et al. Common liability to addiction and "gateway hypothesis": theoretical, empirical and evolutionary perspective. Drug Alcohol Depend 2012;123(S1):S3-17. DOI: 10.1016/j.drugalcdep.2011.12.018.

Results: Smoking and e-cigarette prevalence