This project will use the Multiphase Optimization Strategy (MOST) to guide the development of
optimized treatment strategies for the two most effective smoking cessation medications
(Combination Nicotine Replacement [C-NRT] and varenicline). The investigators will recruit
daily smokers from primary care to participate in a fully crossed, 2x2x2x2 factorial
experiment (N=608) that evaluates 4 different factors: 1) Medication Type (Varenicline vs.
C-NRT), 2) Preparation Medication (4 Weeks vs. Standard), 3) Medication Duration (Extended
[24 weeks] vs. Standard [12 weeks]); and 4) Counseling (Intensive vs. Minimal). Participants
will complete assessments one week pre-quit and then assessments of smoking status, treatment
use, side effects, potential treatment mechanisms (e.g., withdrawal, self-efficacy) during
the first week post-target quit date (TQD) and at Weeks 2, 4, 12, 20, 26, and 52 post-target
quit date. These data will be used to examine the main and interactive effects of these four
factors on various outcomes, with biochemically confirmed 12-month abstinence serving as the
primary outcome. These data will also be used to determine which factors and combinations of
factors are most effective with regard to 12-month biochemically confirmed abstinence and
cost, thereby identifying optimized varenicline and C-NRT treatments, with each developed to
yield especially great benefit. These optimized treatments will then be tested in the
Optimized Care Project. The investigators will also examine the relative effects of each
medication on particular outcomes (e.g., 12-month abstinence).