Nicotine products relative risk assessment: a systematic review and meta-analysis

Background: Nicotine products have been the subject of considerable innovation over the past few decades.  While the health risks of combustible cigarettes and most tobacco-based products are well characterized, there is less clarity regarding newer nicotine products, and how they compare with the traditional forms. Methods: In this study, we have developed a relative risk hierarchy (RRH) of 13 nicotine products based on systematic review of the scientific literature and analysis of the best available evidence. In total, 3980 publications were identified and screened, with 320 studies being carried through to the final analysis. The health risk data for each product was extracted and the level assessed.  The products were analyzed in terms of their toxin emissions and epidemiological data, which were combined on an arbitrary scale from 0 to 100 (low to high risk) to derive a combined risk score for each nicotine product. Results: Combustible tobacco products dominate the top of the RRH, with combined risk scores ranging from 40 to 100. The most frequently consumed products generally score highest. Dipping and chewing tobacco place considerably lower on the hierarchy than the combustible products with scores of 10 to 15, but significantly above heat-not-burn devices and snus, which score between 3 and 4. The lowest risk products have scores of less than 0.25 and include electronic cigarettes, non-tobacco pouches and nicotine replacement therapy. Conclusions: The RRH provides a framework for the assessment of relative risk across all categories of nicotine products based on the best available evidence regarding their toxin emissions and the observed risk of disease development in product users. As nicotine products continue to evolve, and more data comes to light, the analyses can be updated to represent the best available scientific evidence.