We believe these findings warrant larger, adequately powered (and controlled) clinical trials within older adolescent smokers. Interpretation of findings should be tempered by study limitations, most notably the lack of power within the small sample to comprehensively assess safety, tolerability, and efficacy of these medications. While the double-blind sellectchem nature of the randomized treatment was a methodological strength, inclusion of a placebo treatment group would have allowed for additional comparisons. Another concern is poor participant retention, a pervasive challenge in adolescent smoking cessation studies that undermines the ability to detect effects over time. For this reason, we caution readers not to over-interpret abstinence outcomes (Table 2), which are provided for descriptive purposes only.

To address attrition, future studies should incorporate innovative techniques, such as retention-targeted contingency management (Carroll et al., 2006; Festinger, Marlowe, Dugosh, Croft, & Arabia, 2008; Ledgerwood, Alessi, Hanson, Godley, & Petry, 2008; Sinha, Easton, Renee-Aubin, & Caroll, 2003), and should be conservatively powered in anticipation of elevated dropout rates compared with adult studies. Despite these limitations, findings provide a novel addition to the nascent older adolescent smoking cessation pharmacotherapy literature. Varenicline and bupropion XL, never before investigated as cessation treatments in young smokers, appear to be viable candidates for further study based on the present results.

Future studies to comprehensively evaluate their safety, tolerability, and efficacy in older adolescents should incorporate a fully powered sample, a longer course of treatment (12 weeks), and posttreatment follow-up over several months to allow for more direct comparison with the well-established adult smoking cessation pharmacotherapy literature. One would expect, based on findings to date, lower absolute rates of abstinence among older adolescents versus adults, but it is unclear how effect sizes (odds ratios) would compare between these two age groups. What is clear is that, given the prevalence and significant public health impact of older adolescent smoking, as well as the limits of the current cessation evidence base, further studies of Dacomitinib pharmacotherapy for older adolescent smoking cessation will be critical contributions to the field. Funding Medical University of South Carolina Hollings Cancer Center Pilot Research Program and the National Institutes of Health (K12DA000357, K23DA020482, R25DA020537, and UL1RR029882). Declaration of Interests Dr. Upadhyaya is an employee and stockholder of Eli Lilly and Company. The other authors do not have potential conflicts to declare.