The blind spot in the nicotine replacement therapy literature: Assessment of the double-blind in clinical trials

University of Minnesota Duluth, Duluth, Minnesota, United States
Addictive Behaviors (Impact Factor: 2.76). 07/2004; 29(4):673-84. DOI: 10.1016/j.addbeh.2004.02.010
Source: PubMed


While clinical trials of medications often use a double-blind procedure, the integrity of the blind and its relationship to treatment outcome is seldom examined. In this review, 73 double-blind, placebo-controlled clinical trials of the nicotine replacement therapies (NRTs) in smoking cessation were identified. Seventeen articles were found that assessed blindness integrity, demonstrating major variations in the assessment, analysis, and reporting of blindness integrity. Although 12 studies found that subjects accurately judged treatment assignment at a rate significantly above chance, the available literature does not permit definitive conclusions about blindness integrity. Recommendations for the assessment, analysis, and reporting of blindness integrity are made.

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Available from: Thomas James White, Jan 21, 2014
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    • "We showed that in practice, despite longstanding recommendations (e.g. Hughes and Krahn, 1985; Mooney et al., 2004 "
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    ABSTRACT: The placebo effect of a psychoactive drug can be defined as the effect of expecting the drug in the absence of its pharmacological actions. As nicotine is widely believed to be the primary factor driving cigarette smoking, smokers are likely to expect nicotine to alleviate craving and withdrawal. The present review examines the extent to which any observed effects of nicotine, and especially its craving- and withdrawal-reducing effects, can be attributed to placebo. We begin by reviewing studies that examined the placebo effects of nicotine in the laboratory and follow with a review of potential placebo effects that are typically not controlled in placebo-controlled studies of nicotine replacement therapy (NRT). In laboratory studies, nicotine instructions decrease tobacco smoking, craving and/or withdrawal, while nicotine-specific effects have not been consistently reported. In field trials of NRT, there is a general failure to assess smokers’ beliefs regarding their drug assignment. This omission makes it difficult to unequivocally attribute findings of placebo-controlled NRT studies to the physiological effects of nicotine. In sum, our review indicates that the placebo effects of nicotine, and specifically nicotine content expectations, may account for many of the benefits associated with nicotine delivery devices in both laboratory and field studies.
    Full-text · Article · Sep 2014 · Journal of Psychopharmacology
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    • "), including those for treating tobacco dependence (Mooney et al. 2004). "
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    ABSTRACT: Expectancies regarding treatment assignment may influence outcomes in placebo-controlled trials above and beyond actual treatment assignment. For smoking pharmacotherapies, guessing enrollment in the active medication treatment is associated with higher abstinence rates. However, placebo-controlled trials of smoking pharmacotherapies rarely assess perceived treatment assignment and those that do only collect this information after reaching full dosage. To determine the temporal relationship between treatment expectancies and smoking-related variables, we assessed the impact of treatment guess during a placebo-controlled laboratory study of varenicline on measures of craving, smoking reward, and smoking reinforcement. We hypothesized that treatment guess at mid-titration would influence smoking-related measures at full dosage, above and beyond actual medication effects. We also explored factors related to guess stability and differences in blind fidelity between mid-drug titration and full dosage. Eighty-eight participants completed laboratory assessments at baseline, mid-titration, and full dosage that involved self-report and behavioral measures of tonic craving, cue-provoked craving, smoking reward, and smoking reinforcement. Participants guessed treatment assignment at mid-titration and full dosage. Generalized linear models confirmed that, beyond actual treatment assignment, treatment guess improved model fit for both self-report and behavioral smoking-related measures. Further, accuracy of treatment guess improved from titration to full dosage, and specific demographic factors (e.g., gender, race) were associated with type of treatment guess and guess stability across time. These results reinforce the importance of assessing perceived treatment assignment repeatedly during placebo-controlled trials and suggest that treatment expectancies during titration can affect outcomes once full dosage has been reached.
    Full-text · Article · Jan 2014 · Psychopharmacology
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    • "Smokers participating in such trials seem particularly good at identifying when they are receiving a placebo treatment. A review of 73 blinded trials suggested fewer than a quarter (n = 14) reported blindness assessments for their intervention versus control groups, and of these, 71% suffered blindness failure [52]. It should not surprise us that smokers, indeed all affected by drug dependence, might be highly sensitive to the symptoms normally associated with absorption of their preferred drug. "
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    ABSTRACT: A strong body of evidence guides clinical responses to alcohol and tobacco dependence and there is an emerging evidence base informing responses to cannabis dependence. Nevertheless, there are still important gaps in the evidence base. Three researchers, with backgrounds in alcohol, tobacco and cannabis research examine current clinical research and practice to identify potential future priorities for clinical research. Clinical outcomes will be improved by research that enhances engagement and retention of a broader range of consumers, especially underrepresented and disadvantaged populations who may not respond as well to mainstream interventions. Research might focus on innovative client recruitment approaches, varying treatment intensity, use of new technology and assertive outreach. Assessment of treatment outcome will be enhanced by strategies that facilitate longer-term follow up of participants, adoption of shared measures of non-abstinent outcomes and extending the focus and outcome measures beyond drug use. Translation of research into clinical strategies will be enhanced by improving links between theory and interventions, increased attention on factors that influence treatment fidelity, designing treatment studies that are relevant to a variety of clinical settings, focussing on clinician characteristics as treatment variables and developing methodologies that address the capacity of participants to discriminate between placebo and pharmacotherapy. A range of future research priorities have been identified that have the potential to better engage and retain clients in a range of treatment settings and enhance translation of research findings into improved treatment outcomes.
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