Can the blind see? Participant guess about treatment arm assignment may influence outcome in a clinical trial of bupropion for smoking cessation

In a placebo-controlled bupropion smoking cessation trial, we examined blind integrity, the link between blind integrity and quit rates, and whether side effects and changes in nicotine withdrawal symptoms or mood were mechanisms through which blind integrity is threatened. At a 12-month follow-up, 498 participants indicated whether they thought they received bupropion, placebo, or were not sure. Potential mediators of treatment effects on treatment arm guess (i.e., side effects, withdrawal, and mood) were measured during treatment, and 7-day point prevalence cessation was assessed at the end of treatment (EOT) and at 6 and 12 months after quit date. Overall, 55% of participants guessed their randomization correctly. Compared to guessing not sure, participants who guessed they were taking bupropion were more than twice as likely to have been randomized to bupropion. Similarly, participants who guessed placebo were twice as likely to have been randomized to placebo. Treatment arm guess was associated with quit rates. Including treatment arm guess with actual treatment arm in models of quit rates significantly reduced the odds ratio for bupropion efficacy at the EOT and at 6 and 12 months after quit date. There was no evidence for mediation. In bupropion smoking cessation trials, blind failure may occur and participant guess about treatment arm assignment is associated with quit rates.