Combination NRT (cNRT) and varenicline have been identified as the two most effective smoking cessation medications (Cahill et al., 2013; Fiore et al., 2008). In the UW-TTURC trial, the efficacy of cNRT varied with rs16969968 genotypes, representing a pharmacogenetic interaction. In contrast, in the varenicline trial, we found that the efficacy of varenicline did not vary with CHRNA5 genotypes, which then leads to the conclusion that all subjects respond to varenicline regardless of CHRNA5 rs16969968 genotype. These results are based on retrospective analyses of existing trials testing different medications, using dissimilar designs, and showing markedly different clinical success in the placebo arms (e.g., 44% vs. 22% abstinence for GG genotypes in the UW-TTURC and varenicline trials), all of which suggest caution in the interpretation of these pharmacogenetic effects as well as raise the question about why the placebo responses are differing significantly between the two studies.
