Schnoll Robert, Wileyto E Paul, Bauer Anna-Marika, Fox Erica N, Blumenthal Daniel, Hosie Quinn Mackenzie, Leone Frank, Huffman Mark D, Khan Sadiya S, Gollan Jacqueline K, Papandonatos George D, Hitsman Brian
Department of Psychiatry and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States.
Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, United States.
Nicotine Tob Res. 2024 Apr 22;26(5):597-603. doi: 10.1093/ntr/ntad218.
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.
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.
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).
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.
Data come from the trial NCT02378714.
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.
使参与者对随机分组不知情是科学的基石。然而，参与者对自身分组的信念会影响结果。在一项安慰剂对照试验中，我们研究了盲法完整性、试验组信念与戒烟之间的关联，以及在接受伐尼克兰治疗的吸烟重度抑郁症（MDD）患者中，治疗组与治疗组信念之间的潜在机制。
175名参与者在治疗结束时被问及他们认为自己接受的是安慰剂、伐尼克兰还是不确定。我们评估了治疗组信念与实际治疗分配之间的关系，研究了治疗组信念与治疗结束时戒烟之间的关联，并评估了渴望、戒断反应、副作用、抑郁症状和吸烟奖赏的变化，作为治疗组信念产生作用的中介因素。
治疗组信念与实际分组显著相关（χ2(2)=13.0，p=0.002）。与“不确定”相比，伐尼克兰组的参与者认为自己服用伐尼克兰的可能性高出3倍多（相对危险度=3.05[1.41 - 6.60]，p=0.005）。安慰剂组的参与者认为自己服用安慰剂与“不确定”的可能性相同（χ2[2]=0.75，p=0.69）。在控制治疗组因素后，认为自己接受伐尼克兰与戒烟率增加显著相关（比值比=5.91[2.06 - 16.92]，p=0.001）。吸烟奖赏体验的变化可能介导了参与者辨别是否服用伐尼克兰的能力（B=0.077[0.002 - 0.192]，p<0.05）。
接受伐尼克兰治疗的参与者能够辨别自己接受了伐尼克兰，且这种信念与更高的戒烟率相关。需要继续研究参与者如何正确识别自己被分配到伐尼克兰组。
数据来自试验NCT02378714。
本研究补充了关于盲法完整性的稀少文献，特别是在戒烟领域。随机临床试验的参与者能够辨别自己被分配到伐尼克兰组，且认为自己接受伐尼克兰与显著更高的戒烟率相关。识别治疗组分配可能与吸烟奖赏方面的变化有关，而伐尼克兰使用对此已有充分记录。对伐尼克兰分配进行遮蔽具有挑战性。这种药物在临床试验中的效果可能既代表了药理作用，也代表了参与者识别自己正在接受该药物的能力。
