Abstract
BACKGROUND: The substitution of combustible cigarettes (CC) with non-combustible nicotine alternatives, such as e-cigarettes (EC), significantly lowers exposure to harmful chemicals. However, many individuals who use ECs continue smoking CCs, becoming dual users and remaining at increased risk of toxin exposure. This study will examine how the reduction in cigarettes smoked per day (CPD) after switching to ECs correlates with changes in biomarkers of exposure (BoE) and potential harm (BoPH) to evaluate the extent of harm in dual users. METHODS: The study is a prospective, non-randomised, observational, longitudinal cohort study in which 250 CC smokers will be invited to use EC as part of a smoking reduction/cessation strategy. Participants will be grouped in five dual use categories based on the change from baseline in CPD at 1, 3 and 6 months, based on self-reported use in the preceding 30 days. The primary outcome of interest is the mean absolute urinary 2-cyanoethyl mercapturic acid (2CyEMA), a well-validated BoE, also assessed at 1, 3 and 6 months. Other BoE will be assessed, together with exploration of the association between varying intensities of dual use and BoPH. The association between the dual use category and levels of BoE will be evaluated using analysis of variance (ANOVA), in order to understand which BoE are best suited to identifying different levels of dual use. Exploratory assessment of the value of BoPH will similarly be evaluated, to assess whether their predictive power extends from the binary smoker/non-smoker categorization to a more nuanced dual use categorization. The specific details of the own-brand CC will be available once smokers' enrollment in the study is complete. The EC used in the study will be the KIWI 2 Pen refillable pod system, with participants given the option to choose from three different flavored e-liquids: LEAF, MIDWAY, and GLACIAL, all containing 0.9 % nicotine. For specialized equipment used for biomarker analysis please refer our previous publication: https://pubmed.ncbi.nlm.nih.gov/38584934/. CONCLUSION: EC are increasingly adopted as a harm reduction strategy in CC smokers who wish to quit smoking, the outlined Statistical Analysis Plan (SAP) provides a robust approach to understand the impact of EC on CC use and to quantify the impact of dual use on clinical outcomes using BoPH. For statistical calculations we will use R software.