Funding This study was funded by grants DA020810, DA18660, DA14363, DA18267, selleck and DA019951 from the National Institute on Drug Abuse and grants AA11667, AA11822, AA007580, and AA11998 from the National Institute on Alcohol Abuse and Alcoholism. Dr. TJ is also supported by a Merit Review Grant from the Department of Veterans Affairs Medical Research Service. Dr. JFS is also supported by a Career Development Award from the Department of Veterans Affairs Health Services Research and Development Service. Declaration of Interests None declared. Acknowledgments The U.S. Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry.

Numerous organizations have provided invaluable assistance in the conduct of this study, including: Department of Defense, National Personnel Records Center, National Archives and Records Administration, the Internal Revenue Service, National Opinion Research Center, National Research Council, National Academy of Sciences, and the Institute for Survey Research at Temple University. Most importantly, the authors gratefully acknowledge the continued cooperation and participation of the members of the VET Registry and their families.
Cigarette smoking is the single most important cause of preventable morbidity and mortality in the developed world (World Health Organization, 2008). The majority of smokers express a desire to quit, but annually less than 5%�C6% quit and maintain abstinence after 1 year (Hughes, Keely, & Naud, 2004). Pharmacotherapy can at least double quit rates over counseling alone (Fiore et al.

, 2008; Molyneux et al., 2003) but remains underutilized (Shiffman, Brockwell, Pillitteri, & Gitchell, 2008). In part, this may be due to medication management guidelines, which recommend pharmacotherapy be initiated in relation to a fixed quit date (Chambers, 2009; Fiore et al., 2008), with the expectation that cessation will occur at treatment initiation or shortly thereafter. Although setting a quit date is thought to increase the probability of successful quitting (Fiore et al., 2008), we are unaware of empirical tests demonstrating the benefit of this approach. Gradual cessation studies allow smokers to delay setting a quit date until later in the treatment (Hughes, Solomon, Livingston, Callas, & Peters, 2010; Shiffman, Ferguson, & Strahs, 2009), but we are unaware of abrupt cessation studies that have allowed smokers flexible quit dates.

The flexibility to quit at some point during a period of several weeks after treatment initiation may make treatment more acceptable for some smokers. The current study was designed to evaluate whether AV-951 the most recently approved smoking cessation pharmacotherapy��varenicline��could be used successfully with a protocol that allowed smokers to start medication without fixing the quit date as Day 8 of treatment.