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INTRODUCTION The e-cigarette market is large and diverse. Traditional smoking cessation trials involving a control group and a 6-month observation period are an inefficient methodology for testing the multiple treatment options e-cigarettes provide for harm reduction in cigarette smokers. We determined when product substitution occurred in the e-cigarette provision arm of an e-cigarette substitution trial for cigarette smokers who were not interested in quitting. METHODS We conducted a secondary analysis of 120 cigarette smokers with severe mental illness (recruitment 2017-2020) who were given disposable e-cigarettes for 8 weeks and assessed at weeks 0 (t0), 2, 4, 6, and 8. We explored product substitution through visit-to-visit correlations in change in product use, then developed a dual process growth model for cigarette and e-cigarette use to test the association between increases in e-cigarette use and concurrent decreases in cigarettes smoked. RESULTS Mean age of the participants was 45.9 years, and 42.7% smoked >20 cigarettes per day. Almost all product substitution occurred between t0 and t2. For the average smoker (18 cigarettes per day), t2 cigarette frequency decreased by 0.39 (95% CI: -0.56 - -0.22) cigarettes for each additional e-cigarette session. There was effect modification (p=0.033), such that baseline light smokers (<10 cigarettes/day) had no significant decrease in t2 cigarette frequency, regardless of their initial increase in e-cigarette use, while heavy smokers (38 cigarettes/day) switched products nearly on a one-to-one basis. CONCLUSIONS In this study, most product substitution occurred early, and heavier smokers had larger t2 decreases in cigarettes/day with increased e-cigarette use. If confirmed with replication studies, the findings could suggest establishment of a novel outcome for e-cigarette studies - early product substitution - and support the value of short-term comparative effectiveness trials that compare multiple potentially lower harm tobacco products. [ABSTRACT FROM AUTHOR]