July 1, 2016
Department of Medicine, University of California, San Francisco
Key Takeaways
- Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60% after smoking only VLNC cigarettes for six weeks
- After six weeks of smoking VLNC cigarettes, self-reported dependence and daily nicotine intake were lower at the end of the trial compared to the control condition
- Funded by the National Institute on Drug Abuse (NIDA) and FDA Center for Tobacco Products (CTP) (grant id: U54 DA031659) and the National Cancer Institute (NLB) (grant id: R01 CA78603)
Abstract
Background and Aims
Clinical trials on the impact and safety of reduced nicotine content cigarettes (RNCs) are ongoing, and an important methodological concern is participant compliance with smoking only RNCs. Our aims were to measure non-compliance biochemically with urine cotinine (COT) and total nicotine equivalents (TNEs), compare with self-reported non-compliance and identify associated covariates.
Design
Secondary analysis of a double-blind, parallel, randomized clinical trial.
Setting
Research centers from the United States, enrolling participants from June 2013 to July 2014.
Participants
Volunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD).
Intervention
Smoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks.
Measurements
The primary outcome was biochemically verified non-compliance, measured as thresholds of COT/CPD and TNE/CPD ratios, considering changes in nicotine content from conventional levels to VLNCs, and as an absolute threshold of week 6 TNEs. Self-reported non-compliance was measured via daily phone calls. Key predictors included age, sex, race, menthol preference, nicotine metabolite ratio, time to first cigarette, dependence, CPD, TNEs, tar level and cigarette evaluation.
Findings
Estimates of non-compliance with smoking the VLNCs exclusively include: the biochemical ratios (both 78%), the week 6 TNE threshold (76%) and self-report (39%). Of the key covariates, age, dependence and cigarette evaluations of satisfaction were significant; for age, younger participants more likely to be non-compliant [P = 0.01; odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96–0.99]. Dependence was associated significantly with self-reported non-compliance (P = 0.01; OR = 1.28, 95% CI = 1.06–1.55). Cigarette evaluations of satisfaction were associated significantly with non-compliance (P = 0.001; OR = 0.71, 95% CI = 0.61–0.82).
Conclusions
Among smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%.
