Stuart G. Ferguson

Does reducing withdrawal severity mediate nicotine patch efficacy? A randomized clinical trial.

Nicotine replacement therapy (NRT) repeatedly has been shown to improve smoking treatment outcome. The major mechanism posited for this improvement in outcome is that NRT reduces nicotine craving and withdrawal. The authors tested this hypothesized mechanism of action using real-time data on craving and withdrawal, collected by ecological momentary assessments administered on a palm-top computer. Smokers (N = 324) were randomized to receive either active high-dose (35 mg) 24-hr patches or placebo. Increases in positive affect and decreases in craving, negative affect, and attention disturbance severity were related to lower risk of lapsing. Although NRT treatment did significantly decrease withdrawal and craving severity, these reductions only partially accounted for NRTs impact on time to first lapse: The results from a mediation analysis showed that the hazard ratio for NRT, when controlling for withdrawal and craving severity, was only a third to a half lower than the uncontrolled hazard ratio for NRT alone. This suggests that other mechanisms for the effectiveness of NRT need to be examined.

Nicotine patch therapy prior to quitting smoking: a meta‐analysis

AIM To evaluate the incremental efficacy of starting nicotine patch treatment prior to quitting compared to the current regimen of starting patch treatment on the target quit day. DESIGN AND MEASUREMENTS Meta-analysis of four eligible studies using pre-cessation patch treatment, located by database search and contacts with cessation researchers. The studies all compared starting treatment with nicotine patch prior to the target quit date to starting active treatment at the quit date, some in the context of concurrent mecamylamine treatment. The primary end-point for the analysis was continuous abstinence for at least 28 days assessed at 6 weeks following quit day; 6-month outcomes were also examined. FINDINGS Compared to starting active patch treatment on quit day, pre-cessation treatment with nicotine patches was found to double the odds of quitting. This was true both at 6 weeks [pooled odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.31-2.93] and 6 months (pooled OR = 2.17, 95% CI: 1.46-3.22) treatment outcomes. Mecamylamine co-treatment did not modify these effects. CONCLUSIONS Across the four studies analyzed, pre-cessation patch treatment was found to produce a robust increase in quit rates compared to current regimens starting patch at quit day. Pre-cessation patch use represents a promising innovation in smoking cessation therapy with potential beneficial implications for improved public health by further increasing quitting success.

Relationship Between Adherence to Daily Nicotine Patch Use and Treatment Efficacy : Secondary Analysis of a 10-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial Simulating Over-the-Counter Use in Adult Smokers

BACKGROUND It has been reported that the efficacy of acute forms of nicotine replacement therapy, such as nicotine gum and lozenges, improves when sufficient quantities of medication are used. OBJECTIVE This analysis examined whether adherence with daily nicotine patch wear was associated with improved rates of smoking abstinence. METHODS This was a secondary analysis of data from a double-blind study in which subjects were randomized to receive either an active nicotine patch or a placebo patch under simulated over-the-counter conditions. Subjects were asked to complete a daily diary on their patch use and smoking. Logistic regression, controlling for smoking in the first 3 weeks of treatment, was used to evaluate the likelihood of abstinence at 6 weeks as a function of treatment assignment (active vs placebo) and adherence (ie, patch wear for >or=20 of the first 21 days of treatment). The relationship between reported adverse events and adherence was also examined. RESULTS This analysis involved data from 371 subjects, 204 using the active patch and 167 using the placebo patch. The study population was mainly white (87.3%), had a mean age of 42.8 years, a mean weight of 77.3 kg, had been smoking for a mean of 24.4 years, and smoked a mean of 25.2 cigarettes per day. Two hundred fifty-three subjects were classified as adherent. Rates of adherence did not differ significantly between the active and placebo groups (139 [68.1%] and 114 [68.3%], respectively). The likelihood of experiencing an adverse event did not differ significantly between adherent and nonadherent subjects in either group. Among active patch users, 61.5% of nonadherent subjects experienced an adverse event, compared with 59.7% of adherent subjects; among placebo patch users, the corresponding proportions were 41.5% and 43.9%. Among active patch users, the odds of abstinence at 6 weeks were more than 3 times greater for adherent versus nonadherent subjects (53.2% vs 21.5%, respectively; adjusted odds ratio [OR] = 3.25; 95% CI, 1.30-8.09; P = 0.011); no benefit of adherence over nonadherence was seen among users of the placebo patch (16.7% vs 15.1%; adjusted OR = 0.60; 95% CI, 0.16-2.31). The interaction between treatment group and adherence was statistically significant (P = 0.022). CONCLUSION Under conditions simulating over-the-counter use, adherence to daily nicotine patch wear within the first 3 weeks of treatment was associated with an improved likelihood of achieving smoking abstinence at 6 weeks.

Exploring the Viability of Using Online Social Media Advertising as a Recruitment Method for Smoking Cessation Clinical Trials

INTRODUCTION The aim of the present study was to explore the viability of using social media as a recruitment tool in a clinical research trial. Sociodemographic data and smoking characteristics were assessed in 266 participants recruited to investigate the effectiveness of a behavioral support program for smoking cessation. METHODS For analysis, participants were separated into 2 groups based on whether they were recruited either using traditional means (flyers, word of mouth, or newspaper advertisement; n = 125, 47.0%) or by advertisements in online social media (n = 138, 51.9%). RESULTS Participants recruited via social media were significantly younger, but there were no differences in other socioeconomic variables or smoking characteristics compared with participants recruited via other traditional means. CONCLUSIONS The findings of the present study suggest that using online social media is a viable recruitment method for smoking studies and compliments other more traditional recruitment methods.

Tobacco dependence and withdrawal: Science base, challenges and opportunities for pharmacotherapy

Several pharmacotherapies for tobacco dependence and withdrawal have been approved by the Food and Drug Administration to aid smoking cessation. These medicines double to triple the odds of cessation compared to placebo, with the diversity in chemical entity (e.g., nicotine, varenicline, bupropion) and route (e.g., nicotine gum and transdermal patch) providing options for people who find a given medication unacceptable or ineffective. Treatments in development include vaccines, combinations of existing products, and new indications, such as reduced tobacco use and exposure. These therapies have been developed on the foundation of research on the neuropharmacology of tobacco dependence and withdrawal. Ongoing research is expected to contribute to more efficacious use of existing therapies and the development of new approaches. This article addresses these developments as well as the challenges to medication development. Challenges include understanding the population-based and individual differences in the vulnerability to dependence and responsiveness to various treatment options, which could contribute to effective treatment to patient matching. Research on the CNS effects of administration and withdrawal of nicotine and other tobacco product constituents is expanding, providing the basis for more effective therapeutic approaches and new medications development. Additionally, whereas medications are approved on the basis of standardized assessments of efficacy and safety in clinical trials, the public health impact of medications depends also on their appeal to smokers and their effectiveness in actual use settings. Research on more effective medication use along with policies that support improved access and utilization are vital to conquering the tobacco epidemic.

Smokers' Interest in Using Nicotine Replacement to Aid Smoking Reduction

In recent years the public health community has considered the risks and benefits of encouraging smokers to reduce their smoking, perhaps with the aid of nicotine replacement therapy (NRT). Little is known, however, about whether smokers themselves are interested in smoking reduction; whether they see reduction as an endpoint, or primarily as a route to cessation; or whether they are receptive to the notion of using NRT to achieve reduction. We conducted a population-based national telephone survey of 1,000 current daily cigarette smokers (499 male, 501 female). Most smokers (57%) reported previously trying to reduce their smoking, and many (26%) said that they plan to reduce within the next year. Almost half of those planning to quit in the next 12 months (44%) preferred to quit via gradual cessation and most (68%) indicated that they would consider using a reduction product or medication. Respondents reported that they would prefer a product with a cessation endpoint rather than a reduction endpoint (63% vs. 21%). Interest in reduction was highest among smokers who were less interested in quitting and among heavier smokers. We conclude that many smokers are interested in gradually reducing prior to quitting and that promoting reduction is unlikely to undermine motivation to quit smoking.

Providing accurate safety information may increase a smoker's willingness to use nicotine replacement therapy as part of a quit attempt.

AIM Previous studies have reported that smokers who are misinformed about the safety of Nicotine Replacement Therapy (NRT) are less likely to report using it. In this study, we examined whether providing information that counters these concerns might impact on intentions to use NRT. PARTICIPANTS 900 smokers recruited from a market research database. DESIGN AND SETTING Participants completed an online survey that asked about their views about NRT. Smokers with safety and efficacy concerns were queried to determine whether accurate information might increase their interest in using NRT. FINDINGS Misperceptions of NRT safety were common: 93% of smokers did not know that smoking while wearing the nicotine patch does not cause heart attacks; 76% that nicotine gum/lozenge are not as addictive as cigarettes; and 69% that NRT products are not as dangerous as cigarettes. Over half of the smokers with misperceptions reported that they would be more likely to use NRT to help them quit smoking if they were exposed to information correcting their concerns (53%, 58% and 66%, respectively, for each of the misperceptions). CONCLUSIONS These data suggest that while a sizeable proportion of smokers are still misinformed about the safety of NRT, misinformed smokers would increase consideration of NRT if these misperceptions are addressed by corrective information.

Quitting by gradual smoking reduction using nicotine gum: a randomized controlled trial.

BACKGROUND Many smokers express a desire to quit smoking by gradually reducing the number of cigarettes they smoke until they stop completely. This study tested the efficacy of nicotine gum in facilitating cessation through gradual reduction. DESIGN This was a multi-center, placebo-controlled, double-blind RCT of 2- and 4-mg nicotine gum versus placebo. SETTING/PARTICIPANTS 3297 smokers who were interested in quitting gradually. INTERVENTION Subjects were instructed to gradually reduce their smoking while increasing their gum use over the course of up to 8 weeks. Once they had achieved initial abstinence (no smoking for 24 hours), gum was to be used in accordance with the current FDA-approved directions for cessation. The study was conducted under over-the-counter conditions, with no counseling provided. Continuous abstinence was assessed after 28 days and 6 months. Secondary measures of smoking reduction were also assessed. Analyses were conducted in 1999-2000 and 2007-2008. MAIN OUTCOME MEASURES Smokers on active gum were significantly more likely to achieve initial cessation (2 mg: OR=1.42; 4 mg: OR=1.90); 28-day continuous abstinence (2 mg: OR=2.01; 4 mg: OR=4.66); and continuous abstinence at 6 months (2 mg: OR=1.80; 4 mg: OR=5.96). During the reduction phase, active gum aided smoking reduction, and participants who reduced their smoking were more likely to achieve abstinence. CONCLUSIONS These findings demonstrate that smokers who wish to quit smoking by gradual reduction can increase their success by using nicotine gum to facilitate reduction and cessation.

Cue reactivity in non-daily smokers: Effects on craving and on smoking behavior

RationaleNon-daily, or intermittent smokers (ITS), are increasingly prevalent. Their smoking may be more situational than that of daily smokers (DS), and thus is hypothesized to be more influenced by cues.ObjectivesTo assess ITS’ response to cues, and compare it to that of DS.MethodsSamples of 239 ITS and 207 DS (previously reported in Shiffman et al. 2012a) were studied in 2,586 laboratory cue-reactivity sessions. Craving (Questionnaire of Smoking Urges) and smoking (probability, latency, puff parameters, and carbon monoxide increases) in response to cues was assessed following exposure to neutral cues and cues related to smoking, alcohol, negative affect, positive affect, and smoking prohibitions. Mixed effects models, generalized estimating equations and random-effects survival analyses were used to assess response to cues and differences between DS and ITS.ResultsITS’ craving increased following exposure to smoking and alcohol cues and decreased following positive affect cues, but cues had little effect on smoking behaviors. Cue reactivity was similar in ITS and DS. Among ITS, craving intensity predicted smoking probability, latency, and intensity, and the effects on latency were stronger among ITS than DS.ConclusionsContrary to hypotheses, ITS were not more responsive to laboratory cues than DS. Results show that ITS do experience craving and craving increases that are then associated with smoking.

Using the Methods of Ecological Momentary Assessment in Substance Dependence Research - Smoking Cessation as a Case Study

Ecological momentary assessment (EMA) is the name applied to any of a range of research methodologies that aim to assess participants in near real time as they go about their regular day-to-day activities. Such methods have particular utility for studying drug use and drug dependence. Using the area of nicotine dependence as a case study, this review highlights how EMA can be used to build upon the findings from more traditional research methods to enhance our understanding of drug use. Particular attention is given to the role that advances in technology have played in the adoption of EMA in drug dependence research.