Our findings demonstrate the significant difference in the CHRNA5 genetic effect on abstinence at end of treatment in the placebo groups in two cessation trials. This difference across the two trials is likely due to heterogeneity in study design such as ascertainment, placebo conditions, and counseling effects. This difference in placebo groups substantially alters the interpretation and comparison of pharmacogenetic effects of two highly effective smoking cessation pharmacotherapies (cNRT and varenicline). Comparison of results from these two important trials highlights the need for a head-to-head comparison trial with a uniform placebo control to compare the pharmacogenetic effects related to both pharmacotherapies. No randomized trial has yet compared the efficacy of varenicline and cNRT with the same placebo control (Rigotti, 2013). Thus, the current results are intriguing and suggest caution in extrapolating research findings into clinical practice.
