Prospective longitudinal studies mainly conclude on a causal role of e-cigarettes in the initiation of cigarettes in flagrant contradiction with conclusions drawn from epidemiology and other studies showing a sharp decline in cigarette use in parallel with the spread of e-cigarette use. This systematic review explores the reasons for this discrepancy.
Methods: Among 84 publications on e-cigarette/cigarette association in adolescents identified in the Medline database from 2011 to 2022, 23 concern 22 never-smoker longitudinal sub-cohorts.
Results: A link between e-cigarette experimentation at T1 and cigarette initiation at T2 is reported in sub-cohort analyses of never-smokers (AOR: 1.41 to 8.30). However, studies exclude 64.3% of T1 e-cigarette experimenters (because of dual-use) and 74.1% of T2 cigarette experimenters. With this study design, e-cigarettes contribute only to 5.3% of T2 cigarette experimentation, casting major doubt on the external validity of results and authors' conclusions that e-cigarettes have a significant effect on the initiation of cigarettes (Gateway effect) at the population level. This sub-cohort design prohibits highlighting any Diversion effect, which is the most likely mechanism accounting for the competition between these two products.
Conclusions: While nicotine abstinence remains the best medical option, over-regulation of e-cigarettes because of misinterpretation of longitudinal study results may be detrimental to public health and tobacco control.
Keywords: adolescents; cigarette; diversion effect; e-cigarette; gateway effect; longitudinal study; selection bias; systematic review.