Seeing Through the Blind: Belief About Treatment Randomization and Smoking Cessation Outcome Among People With Current or Past Major Depressive Disorder Who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION

Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial.

AIMS AND METHODS

175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed.

RESULTS

Treatment arm belief was significantly associated with actual arm assignment (χ2(2) = 13.0, p = .002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, versus "not sure" (RR = 3.05 [1.41-6.60], p = .005). Participants in the placebo arm were just as likely to believe they were taking placebo versus "not sure" (χ2[2] = 0.75, p = .69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR = 5.91 [2.06-16.92], p = .001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline (B = 0.077 [0.002-0.192], p < .05).

CONCLUSIONS

Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

TRIAL REGISTRATION

Data come from the trial NCT02378714.

IMPLICATIONS

The present study adds to the sparse literature on blind integrity, particularly in the field of tobacco cessation. Randomized clinical trial participants can discern their assignment to varenicline, and believing that one received varenicline was associated with significantly higher cessation rates. Identifying treatment arm allocation may be associated with changes in the rewarding aspects of smoking that have been well documented with varenicline use. Masking allocation to varenicline is challenging. The effects of this medication in clinical trials may represent both pharmacological effects and participants' abilities to recognize that they are receiving the medication.