The eligibility criteria for Studies 1 and 2 were: (a) use ST daily (��6 dips/day) for the past 6 months, (b) apparent good health with no unstable medical condition, (c) good mental health, (d) no contraindications to nicotine replacement use, (e) not using other tobacco products, and (f) not pregnant or nursing. Studies 3 and selleck chemicals 4 changed the required ST use to ��2 tins/week and kept all other eligibility criteria. Study 5 required the use of at least one tin of moist snuff per week for a minimum of 1 year and additionally subjects could not be currently using any methods for quitting tobacco or cutting down on tobacco use. The sample sizes for the studies were: Study 1 (N = 66), Study 2 (N = 106), Study 3 (N = 102), Study 4 (N = 199), and Study 5 (N = 41).

All studies collected data from two baseline visits that were one week apart. (Subjects attended two baseline visits in order to determine reliability of our measures, to reduce subject burden of completing several questionnaires at each visit, and to collect subject diaries on ST use between visits). During each baseline visit, subjects provided a urine sample for cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL, a biomarker for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or NNK, a potent lung carcinogen) analyses and completed a questionnaire regarding tobacco use history. Statistical Methods Flavors were placed into two categories: No Flavor (Classic, None, Straight) or Mint Flavor (Ice, Mint, Spearmint, Wintergreen). Subjects with missing data on current brand flavor (n = 12) were excluded.

Additionally, those who reported ever using fruit-flavored ST products were excluded due to the small sample size (n = 34). Between-study heterogeneity was assessed by testing the differences in demographic and tobacco use variables across the five studies, using Chi-squared, Fisher��s exact and Kruskal�CWallis tests as appropriate. Significant differences between the five studies were found, most notably in age, ST use patterns, and biomarker levels. The number and proportion of users of mint-flavored ST products (yes/no) were described over the course of use (first product, first regular product, first daily product, and current product). We compared the first ST product used (mint/no flavor) with the current product used to determine whether the first product influenced the current product choice.

The proportions of subjects switching products were compared using a Z-test. Demographic and tobacco use variables, including age at first dip and regular use, amount of use, duration of use, and measures of dependence (e.g., time to first dip, duration of use during the day, number of quit attempts) were summarized by flavor (mint, no flavor). Differences between flavored AV-951 and nonflavored users, in biomarkers of exposure, were also determined. The urine biomarker outcomes of interest for this study were total NNAL (pmol/ml) and cotinine (ng/ml).