title: Estimations and predictors of non-compliance in switchers to reduced nicotine content cigarettes.
abstract: 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.
  
  
  
  Secondary analysis of a double-blind, parallel, randomized clinical trial.
  
  
  
  Research centers from the United States, enrolling participants from June 2013 to July 2014.
  
  
  
  Volunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD).
  
  
  
  Smoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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%.
authors.affiliation: University of California, San Francisco, Department of Medicine, San Francisco, CA, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Nardone
authors.affiliation: University of Pittsburgh, Department of Psychology, Pittsburgh, PA, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.affiliation: University of Minnesota, Department of Psychiatry, Minneapolis, MN, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.affiliation: University of Minnesota, School of Public Health, Minneapolis, MN, USA.
authors.forename: Joseph S
authors.identifier: 0000-0001-6147-3168
authors.initials: JS
authors.lastname: Koopmeiners
authors.affiliation: University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics, Minneapolis, MN, USA.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.affiliation: University of Pennsylvania, Department of Psychiatry, Philadelphia, PA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Strasser
authors.affiliation: Brown University, Department of Psychiatry and Human Behavior, Providence, RI, USA.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Tidey
authors.affiliation: Johns Hopkins University, Department of Psychiatry and Behavioral Sciences, Behavioral Pharmacology Research Unit, Baltimore, MD, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Vandrey
authors.affiliation: University of California, San Francisco, Department of Medicine and Bioengineering and Therapeutic Sciences, San Francisco, CA, USA.
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D005731:Ganglionic Stimulants / Q000032:analysis*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009538:Nicotine / Q000032:analysis*; D010349:Patient Compliance; D012463:Saliva / Q000737:chemistry; D000074264:Smoking Reduction / Q000379:methods* / Q000523:psychology; D062789:Tobacco Products; D016482:Urinalysis / Q000379:methods
chemical_list: D015415:Biomarkers; D005731:Ganglionic Stimulants; D009538:Nicotine
keywords: Biomarkers; cigarette smoking; cotinine; nicotine reduction; reduced nicotine content cigarettes; total nicotine equivalents