For continuous abstinence at the end of treatment, the OR of 5.9 in favor of varenicline is toward the mid-to-upper end of ORs observed in previously published smoking cessation randomized, placebo-controlled clinical trials of varenicline with a similar dose regimen and treatment duration (OR range: 2.3�C8.4; Gonzales et al., during 2006; Jorenby et al., 2006; Nakamura et al., 2007; Oncken et al., 2006; Rigotti et al., 2010; Tashkin et al., 2010; Tsai et al., 2007; Wang et al., 2009). The difference was maintained through 24 weeks, with the OR of 4.4 being close to the upper value of the range for ORs of previously published clinical trials of varenicline (OR range: 1.9�C4.9; Gonzales et al., 2006; Jorenby et al., 2006; Nakamura et al., 2007; Oncken et al., 2006; Rigotti et al., 2010; Tashkin et al.

, 2010; Tsai et al., 2007; Wang et al., 2009). Continuous abstinence for varenicline of 53.1% for Weeks 9�C12 is in the mid range of continuous abstinence observed in previous studies of varenicline (range: 42.3%�C65.4%), as is the continuous abstinence of 34.7% for Weeks 9�C24 (range: 25.8%�C46.8%; Gonzales et al., 2006; Jorenby et al., 2006; Nakamura et al., 2007; Oncken et al., 2006; Rigotti et al., 2010; Tashkin et al., 2010; Tsai et al., 2007; Wang et al., 2009). One potential drawback of allowing smokers to delay setting a quit date until after starting pharmacotherapy might be an increased probability of the smoker postponing the quit attempt indefinitely. However, in this study, 80.6% of varenicline and 73.3% of placebo subjects reported making a quit attempt during the quitting window.

The number of subjects who made a quit attempt during the treatment phase is actually higher because there are some subjects (44 [9.1%] receiving varenicline and 7 [4.2%] receiving placebo) who were abstinent during Weeks 9�C12 but did not report an attempt in the quit window. These subjects either made their first Entinostat quit attempt outside the quit window (during Weeks 6�C9) or failed to report it during the quit window. Thus, the vast majority of subjects made a quit attempt during the first 9 weeks of the study. The median time to quit attempt in the varenicline group in this flexible protocol was longer than in the traditional fixed quit date protocol (17 vs. 8 days), assuming that everybody in the previous studies made a quit attempt on Day 8, as required by the protocol. However, this extended time to quit date did not appear to result in lower efficacy than that observed in previous studies with a similar population (Gonzales et al., 2006; Jorenby et al., 2006).