First, the NARS trial protocols defined prolonged cessation as commencing from 6 weeks after enrollment to multiple points in follow-up. It seems unlikely that participants recruited based on their not intending to stop smoking in the next month would begin a cessation attempt within selleck 6 weeks of making such a statement. Consequently, such outcomes were rare (occurring in 1.6% of those in the NRT arm; Wang et al., 2008), and trials using this outcome as the primary one would need to be unfeasibly large to show a difference in abstinence between arms. These studies treated smokers for up to 18 months with a view to inducing abstinence throughout that period. It is illogical to treat someone for 18 months but use an outcome measure that counts as a failure anyone who quit after 6 weeks.

One possible solution is to assess the outcome as prolonged abstinence from the end of the treatment period for a further 6 months. This approach also creates problems. First, some smokers will have stopped smoking early in treatment, remained abstinent for a year, but then resumed smoking. If only lifetime abstinence counts as a success, then this is not a problem in itself, but it does reduce the absolute abstinence rate that an intervention achieves. Second, if treatment persists for a year, then successes measured at the 18-month follow-up will be those subjects who have abstained for 6�C18 months. Around 20%�C30% of people who maintain abstinence for 6 months will relapse in the next 12 months (Stapleton, 1998). This finding has two consequences for such a trial.

The sample size is inflated because the outcome (6- to 18-month abstinence) is less frequent than is 6-month abstinence, and, in health economic assessment, lifetime abstinence is the true outcome of interest (Wang et al., 2008). Abstinence lasting 6�C18 months is hard to convert to lifetime abstinence because this mixture of abstinence periods makes relapse rates harder to model. Third, it creates practical problems for researchers. For good reasons, we use a procedure in smoking cessation studies that counts as smokers those who are lost to follow-up (West et al., 2005). Although treatment was offered for 18 months, many participants did not stay with it that long, including many who stopped smoking and used NRT only a few months after stopping, as most quitters do.

To be counted as abstinent such a trial participant would need to GSK-3 continue attending the clinic for the sole benefit of the researcher. Persuading participants to attend repeatedly would be difficult and expensive and risk having participants default from follow-up and be counted as smokers when they are in fact abstinent. Evidence indicates that repeated assessments without therapeutic benefits reduce follow-up rates (Velicer et al., 1999).