primarily metabolized by the CYP2B6 enzyme (23, 24). Instead of using NMR, this study presents the first genotype by NRT interaction with a proper placebo-control arm. Our findings differ from earlier reports primarily because we found that nicotine metabolism did not predict cessation outcome amongst persons given NRT which appears to neutralize the relapse risk associated with faster nicotine metabolism. At present, it is difficult to resolve the differences between study findings due to differences between subjects and experimental conditions. These differences highlight important methodology considerations: 1) Some of the prior studies did not include a placebo arm, which is needed to determine a gene × medication interaction, 2) NRT and bupropion were often not included in the same trial, and 3)In the current trial the same behavioral counseling was used in all medication conditions, whereas the effects of counseling could vary across trials which is a possibility based on observed differing abstinence rates in placebo arms of different trials. While future meta-analyses can be helpful, caution should be used as differences in ascertainment, treatment intensity, assessment, and treatment comparisons across trials can result in problematic interpretations (25, 26).
