18. Lastly, we decided against a factorial design that would have included slow metabolizers of nicotine in this trial and thus, cannot discern that the ROCK1 present effects are unique to fast metabolizers of nicotine. Nevertheless, the present study provides an indication that high dose transdermal nicotine may increase abstinence rates among fast metabolizers of nicotine and that this treatment approach is likely to be safe. It is worth noting how the present results compare to a previous study which compared 21 mg and 42 mg nicotine patches but did not restrict eligibility to fast metabolizers of nicotine (Kalman et al., 2004). In contrast to the present results and contrary to expectation, Kalman et al. (2004) found higher quit rates (p < .08) among the 21 mg nicotine patch group, compared with 42 mg, at the end-of-treatment.

An increase in adverse events among participants in the 42 mg dose condition was postulated as a possible explanation for the finding, a result that may have occurred from the inclusion of slow metabolizers of nicotine who received 42 mg nicotine patches. The current sample size, however, was small and the results concerning treatment arm effects on abstinence rates were significant only at Week 1 and then approached statistical significance at Week 8. Thus, the results should only be interpreted to provide support for the need to conduct an adequately powered clinical trial of high dose transdermal nicotine for fast metabolizers of nicotine.

Such a trial is recommended, given the paucity of efficacious treatments for these smokers, who may represent 75% of the population distribution of smokers, and the possibility that such a trial may yield information essential for guiding a personalized treatment for nicotine dependence. Supplementary Material Supplementary Table 1 can be found online at http://www.ntr.oxfordjournals.org. Funding This research was supported by grants from the National Institute on Drug Abuse (NIDA; R21 DA026889, R01 DA025078, P30 DA12393), by a grant from the NIDA and the National Cancer Institute (NCI; P50 CA143187), and by a grant from the NIDA, the NCI, the National Institute of General Medical Sciences, and the National Human Genome Research Institute (U01 DA020830). Declaration of Interests Dr. RAS has served as a consultant to GlaxoSmithKline, the company that manufactures the nicotine patch used in this study.

However, GSK did not provide medication or financial support for this study. Dr. RFT has shares in Nicogen Research Inc., a company focused on novel Brefeldin_A smoking cessation treatment approaches. Dr. RFT has also consulted for Novartis and McNeil pharmaceuticals on smoking cessation approaches. Dr. NLB serves as a consultant to pharmaceutical companies that market smoking cessation medications and has served as a paid expert witness in litigation against tobacco companies.