TSRC, Tob. Sci. Res. Conf., 2016, 70, abstr. 56

Randomized controlled trial methodological considerations for evaluating exposure from cigarettes and e-vapor products use under ad libitum ambulatory conditions

EDMISTON J.(1); ZHAO Y.(2); LIANG Q.(1); LIU J.(1); DUHON C.(1); SARKAR M.(1)
(1) Altria Client Services LLC, Richmond, VA, USA; (2) Eurofins Lancaster Laboratories PSS, c/o Altria Client Services LLC, Richmond, VA, USA

Introduction: The purpose of this study was to understand methodological considerations for a randomized controlled trial (RCT) designed to evaluate exposure and product use in adult smokers (AS) using e-vapor products under ad libitum conditions. Method: AS (age 21-65) included in this study were generally healthy, smoked 10 or more cigarettes per day (CPD) and were not intending to quit in the next 30 days. Participants were allowed to try the test products (MarkTen® e-cigarettes, Menthol and Classic {1.5% by weight USP grade tobacco derived nicotine, 3.7 volt battery, approximately the size of a King Size traditional cigarette}) and complete purchase interest and product flavor ranking questionnaires. Participants that indicated they “might/might not”, “probably” or “definitely” would buy the test product were enrolled into the study. After one week of baseline assessments, 148 participants were randomized into Control Group (CG, n=45) or Test Group (TG, n=103) for a 4-week product use period. Participants in the TG were allowed to use their higher ranked test product based on flavor preference and their own cigarettes ad libitum; the CG continued smoking their own cigarettes ad libitum. CPD and MarkTen® test product use were tracked daily with an Interactive Voice Response System (IVRS). Blood and spot urine samples for biomarkers of exposure (BOEs: NNAL, Nicotine Equivalents, COHb) were collected at weekly afternoon clinic visits. Results: On average, by the end of the study, participants in the TG used approximately one MarkTen® cartridge per day [range: 0-8] and their CPD change from baseline (-18.5%) was statistically significantly different compared to the CG (+4.29%) (p<0.0001). Approximately 15% of the TG reduced their average CPD by 50% or more (3 participants reported 100% reduction in CPD) for the last week of the study compared with no participants in the CG. Although all BOEs tended to be lower in the TG compared with the CG, none of the differences was statistically significant (p<0.05) and high inter-subject variability was observed in all BOEs (CV range: 37.7-107%). On average, subjects in the TG that indicated they “definitely” would buy the test products (n=26) used more cartridges per day (1.4 cartridges per day) and reduced their CPD more (-4.39 CPD) compared to subjects that indicated they “probably” (n=44, 0.92 cartridges per day, -3.24 CPD) or “might/might not” (n=27, 0.81 cartridges per day, -1.66 CPD) buy the test products. Conclusions: These results suggest that, on average, AS (who are not intending to quit smoking) reduce their CPD when using MarkTen® e-cigs and three AS even stopped smoking while using MarkTen® e-cigs. In addition, questionnaires related to purchase interest and flavor preference may help identify subjects that are more likely to adopt and regularly use the test products under ad libitum ambulatory conditions in a RCT.