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

Abstract

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 post 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 EOT and at 6-and 12-months post 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.

Perceived Treatment Assignment and Smoking Cessation in a Clinical Trial of Bupropion Versus Placebo

“…Th e nonsignifi cant associations between perceived treatment assignment and smoking abstinence at Week 7 and Week 26 are in contrast to previous studies ( Schnoll et al, 2008 ;Th omas et al, 2008 ). Th ese studies found an association between perceived treatment assignment and smoking abstinence at each timepoint assessed.…”

“…However, only two studies investigated the impact of perceived treatment assignment on smoking abstinence in doubleblind, randomized, clinical trials of bupropion (Schnoll et al, 2008;Thomas et al, 2008). Both trials included smokers who consumed at least 10 cigarettes per day (cpd).…”

Treatment Assignment Guesses by Study Participants in a Double-Blind Dose Escalation Clinical Trial of Saw Palmetto

“…16 The finding that participant perception that they were on the experimental therapy, saw palmetto, was correlated with a greater improvement in AUA-SI, is consistent with other reports that have shown a relationship between a beneficial effect on an outcome measure and an increase in the correct perception of treatment assignment. [16][17][18] In a placebo-controlled trial of bupropion as a smoking-cessation agent, participants who guessed that they were on the active agent were more likely to quit smoking than those who guessed they were on placebo or were unsure. 17 In a trial of risperidone in children with autism, health care providers associated the active agent with patient improvement.…”

“…[16][17][18] In a placebo-controlled trial of bupropion as a smoking-cessation agent, participants who guessed that they were on the active agent were more likely to quit smoking than those who guessed they were on placebo or were unsure. 17 In a trial of risperidone in children with autism, health care providers associated the active agent with patient improvement. 16 In a study that compared vertebroplasty with a control intervention in the treatment of osteoporotic vertebral compression fractures, participants assigned to the control intervention who guessed that they received vertebroplasty had greater pain relief at days 14 and 30 than those who guessed that they received the control intervention.…”

CONSORT 2010 Statement—unfinished update?

“…Most importantly insufficient blinding might violate the integrity of a study and can bias results [20]. An example of a pharmacological intervention where the blinding is violated is described in detail by Schnoll et al [21], but this example might be the tip of an iceberg because the assessment of blinding is not frequently reported in clinical trials [6]. The CONSORT group has stopped advocating testing for blinding in the 2010 Statement.…”