The eight RCTs exhibit similar design features and ascertainment criteria, but differ in prevalence of baseline variables and EOT and 6MO abstinence (Table 1 and see Tables, Supplemental Digital Contents 1–4). RCT 5 was conducted in a health care setting [57], and the other RCTs were conducted at Universities. All RCTs were conducted in United States metropolitan regions. Two RCTs were designed as pharmacogenetic efficacy trials [56], one RCT was designed as a comparative effectiveness trial [57], and the remaining RCTs were designed as comparative treatment efficacy trials [58,59,60,61,62]. All RCTs required ≥10 CPD and age >18 years, although one RCT was focused on older smokers [59]. All RCTs had similar exclusion criteria that included reproductive/lactation criteria for females, severe current cardiovascular, neurological, or psychiatric disorders, medical contraindications for pharmacotherapy treatment, and current use of psychiatric drugs. All RCTs provided multiple sessions of group or individual counseling, where one RCT randomized participants to web-based counseling, proactive telephone-based counseling, or both modalities [57]. Therapy randomization from baseline to EOT was to five different pharmacotherapies [NRT, BUP, PLA, VAR or combined NRT
