According to article 32 of the World Medical Association’s Ethical Principles for Medical Research Involving Human Subjects, “the effectiveness of a new intervention must be tested against those of the best current proven intervention.”2 The use of a placebo is only acceptable in studies in which no current proven intervention exists. However, nicotine replacement therapy and bupropion were available interventions recommended by international evidence-based guidelines as first-line pharmacologic treatments for smoking cessation in patients with respiratory disease.3 For example, an earlier trial in patients with COPD, notably, conducted by Tashkin et al4 as well, had shown that smokers who received bupropion for smoking cessation achieved higher continuous abstinence rates than smokers treated with placebo. Furthermore, two large-scale trials5,6 had clearly shown the greater benefit of varenicline compared with placebo and bupropion in the general smoking population—1 year before the current trial by Tashkin et al was initiated. The trial by Tashkin et al is the first to investigate the efficacy of varenicline in patients with COPD, but the authors do not provide compelling and scientifically sound methodologic reasons that justify the use of a placebo control instead of existing evidence-based smoking cessation medication. They only state that smokers with COPD have higher levels of nicotine dependence and are “more resistant to smoking cessation interventions” than smokers without COPD, but this is true for other subtypes of smokers as well, for example smokers with a lower socioeconomic background.