The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT) of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows:
I Adherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype), compared to one tailored to nicotine dependence questionnaire score (phenotype).
II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype.
An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily) using National Health Service (NHS) stop smoking services in primary care are randomly allocated to one of two groups:
i. NRT oral dose tailored by DNA analysis (OPRM1 gene) (genotype), or
ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype)
The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95% confidence interval for observed between-arm difference in mean NRT consumption (Hypothesis I). Motivation to make another quit attempt will be compared between arms in those failing to quit by six months (Hypothesis II).
This is the first clinical trial evaluating the behavioural impact on adherence of prescribing medication using genetic rather than phenotypic information. Specific issues regarding the choice of design for trials of interventions of this kind are discussed.
Funder: Medical Research Council (MRC)
Grant number: G0500274
Date trial stated: June 2007
Expected end date: December 2009
Expected reporting date: December 2010
Using nicotine replacement therapy (NRT) while still smoking in the lead up to quitting could enhance success at quitting, one of the most cost-effective means of improving health, but little is known about its acceptability and tolerability.
To test the acceptability and tolerability of using NRT while smoking for two weeks before quitting, to inform a randomised controlled trial of pre-quitting NRT versus usual NRT-based quitting practice.
Prospective pragmatic uncontrolled clinic-based pilot study in which 14 adult smokers recruited from a smoking cessation clinic were prescribed nicotine patches or gum with follow up for two weeks. Data were collected on participants' concerns about smoking while using NRT, importance of quitting, urges to smoke, smoking behaviour, previous NRT use and the length of the pre-quitting period. Urine tests were collected weekly for cotinine, and participants recorded smoking activity and noted experiences and changes in their health in diaries.
Only 21% of 14 participants expressed concerns about using NRT while smoking. All of the nine followed up used it as recommended, 56% of these reporting no unpleasant symptoms. Median urine cotinine levels declined over the two weeks. Urges to smoke averaged 1.8 on a 4-point scale. All participants decreased the number of cigarettes per day. Diary records showed wide variation in smoking and NRT use, with an increased sense of control and determination to quit.
Smokers using pre-quitting NRT over two weeks appeared to titrate nicotine levels and symptoms of toxicity were uncommon and of low intensity.
Improving and targeting nicotine replacement therapy (NRT) are cost-effective strategies for reducing adverse health consequences for smokers. Treatment studies document the efficacy of precessation NRT and support important roles for level of nicotine dependence and precessation smoking reduction in successful quitting. However, prior work has not identified the optimal precessation dose or means for personalizing NRT. Genome-wide association has identified groups of genomic markers associated with successful quitting, allowing us to develop a v1.0 “quit-success” genotype score. We now report influences of v1.0 quit-success genotype score, level of dependence and precessation smoking reduction in a smoking cessation trial that examined effects of 21 versus 42 mg/24 h precessation NRT. Four hundred seventy-nine smokers were randomized to 21 or 42 mg NRT, initiated 2 wks prior to target quit dates. We monitored self-reported abstinence and end–expired air carbon monoxide (CO). Genotyping used Affymetrix arrays (Santa Clara, CA, USA). The primary outcome was 10-wk continuous smoking abstinence. NRT dose, level of nicotine dependence and genotype scores displayed significant interactive effects on successful quitting. Successful abstinence also was predicted by CO reductions during precessation NRT. These results document ways in which smoking cessation strategies can be personalized based on levels of nicotine dependence, genotype scores and CO monitoring. These assessments, taken together, can help match most smokers with optimal NRT doses and help rapidly identify some who may be better treated using other methods.
This study examined if 2-week free nicotine replacement therapy (NRT) would be more effective than 1-week free NRT to help smokers quit smoking at 6 and 12 months. In a single-blinded randomized controlled trial design, 562 Chinese smokers who attended a smoking cessation clinic in Hong Kong, China, were randomly allocated into two groups (A1 and A2): A1 (n = 284) received behavioural counselling with free NRT for 1 week; A2 (n = 278) received similar counselling with free NRT for 2 weeks. All subjects received printed self-help materials to support their quitting efforts. A structured questionnaire was used for data collection, including pattern of NRT use and self-reported 7-day point prevalence quit rate at 6 months and 12 months. Among the participants, the mean number of cigarettes smoked per day was 18.8 (SD = 10.9). By intention-to-treat analysis, 7-day point prevalence quit rates were not significantly different between A1 and A2 groups at 6-month (27.5% versus 27.3%; P = 0.97) and 12-month (21.1% versus 21.2%; P = 0.98) followup. The findings suggest that two-week free NRT was not more effective than 1-week free NRT to increase smoking cessation rate among Chinese smokers.
Abilities to successfully quit smoking display substantial evidence for heritability in classic and molecular genetic studies. Genome-wide association (GWA) studies have demonstrated single-nucleotide polymorphisms (SNPs) and haplotypes that distinguish successful quitters from individuals who were unable to quit smoking in clinical trial participants and in community samples. Many of the subjects in these clinical trial samples were aided by nicotine replacement therapy (NRT). We now report novel GWA results from participants in a clinical trial that sought dose/response relationships for “precessation” NRT. In this trial, 369 European-American smokers were randomized to 21 or 42 mg NRT, initiated 2 wks before target quit dates. Ten-week continuous smoking abstinence was assessed on the basis of self-reports and carbon monoxide levels. SNP genotyping used Affymetrix 6.0 arrays. GWA results for smoking cessation success provided no P value that reached “genome-wide” significance. Compared with chance, these results do identify (a) more clustering of nominally positive results within small genomic regions, (b) more overlap between these genomic regions and those identified in six prior successful smoking cessation GWA studies and (c) sets of genes that fall into gene ontology categories that appear to be biologically relevant. The 1,000 SNPs with the strongest associations form a plausible Bayesian network; no such network is formed by randomly selected sets of SNPs. The data provide independent support, based on individual genotyping, for many loci previously nominated on the basis of data from genotyping in pooled DNA samples. These results provide further support for the idea that aid for smoking cessation may be personalized on the basis of genetic predictors of outcome.
Tobacco smoking is the leading preventable cause of morbidity and mortality in Australia and other developed countries. Of the pharmacological aids that are available for smoking cessation, bupropion (Zyban SR) is eligible for public reimbursement on the Australian Pharmaceutical Benefits Scheme (PBS), whereas nicotine replacement therapy (NRT) is not. Information on the cost‐effectiveness and financial impact of public reimbursement of these strategies can better inform debate about their inclusion or exclusion in public reimbursement schemes.
To estimate the cost‐effectiveness of bupropion and NRT, and the potential financial impact of public reimbursement of NRT in Australia.
A cost‐effectiveness analysis using a deterministic Markov model, and cost per disability‐adjusted life year (DALY) averted over a lifetime as the outcome measure.
Current smokers, motivated to quit, in Australia in 2000.
(1) NRT; (2) bupropion; and (3) a combined strategy using bupropion as the first‐line treatment and NRT in those who fail to quit smoking or have adverse reactions to bupropion.
Quitting smoking can increase life expectancy of current smokers by 1–7.6 years depending on age at cessation and sex. Providing bupropion to current smokers who are motivated to quit would cost A$7900 (95% uncertainty interval A$6000 to A$10 500) for each DALY averted; NRT patches would cost A$17 000 (A$9000 to A$28 000) for each DALY averted, with similar results even if used as a second‐line treatment following initial failure to quit using bupropion. If 6% of current smokers were to use NRT following inclusion on the PBS, this would result in an annual cost of A$40–110 million to the PBS depending on the listed price.
Compared with other drugs included on the PBS, bupropion and NRT are both highly cost‐effective smoking cessation interventions, and including NRT on the PBS would have a moderate financial impact. Given the sizeable health burden of smoking, and the large individual benefits of quitting smoking, increasing the availability of alternative aids and uptake of these strategies through public reimbursement would be a positive and rational step towards further reducing tobacco‐related disease burden in Australia and other countries where NRT is currently not subsidised.
This secondary analysis examined the association between adherence to nicotine replacement therapy (NRT) and smoking cessation among pregnant smokers enrolled in Baby Steps, an open-label randomized controlled trial testing cognitive-behavioral therapy (CBT) versus CBT plus NRT.
The analysis included only women who received NRT for whom we had complete data (N = 104). Data came from daily calendars created from recordings of counseling sessions and from telephone surveys at baseline and 38 weeks gestation.
Overall, 29% of the 104 women used NRT for the recommended 6 weeks and 41% used NRT as directed in the first 48 hr after a quit attempt. Ordinal logistic regression modeling indicated that using NRT as directed in the first 48 hr and having made a previous quit attempt were the strongest predictors of longer NRT use. Univariate analyses suggested that primigravid women and women who used NRT longer were more likely to report quitting at 38 weeks gestation.
Findings indicated that adherence to NRT is low among pregnant smokers, but adherence was a predictor of cessation. Future trials should emphasize adherence, particularly more days on NRT, to promote cessation during pregnancy.
OBJECTIVE: To estimate the impact of allowing non-prescription sales of nicotine medications in the United States on increasing the numbers of smokers quitting. DESIGN: Sales and marketing data were used to compare the use of nicotine medications before and after non-prescription sales, and to estimate the impact of non-prescription sales on quit rates. SETTING: United States. MAIN OUTCOME MEASURES: Number of quit attempts using nicotine replacement therapy (NRT) products, number of smokers who quit smoking with over-the-counter (OTC) NRT or with NRT still sold by prescription, and incremental quits attributable to OTC NRT. RESULTS: Since the US Food and Drug Administration approved nicotine medications for OTC sale in 1996, use of the medications has increased by 152% compared with prior prescription use. With increased use of an efficacious treatment, OTC nicotine medications are estimated to yield from 114,000-304,000 new former smokers annually in the United States. CONCLUSIONS: The broader availability and promotion of effective treatments for tobacco dependence, specifically nicotine gum and patch, increase the number of smokers availing themselves of the medications. This increased use is estimated to contribute substantially to the number of former smokers in the United States.
Smoking is common in young people, particularly in disadvantaged groups, and continued smoking has a major impact on quality and quantity of life. Although many young smokers want to stop smoking, little is known about the design and effectiveness of cessation services for them.
To determine whether nicotine replacement therapy (NRT) when combined with counselling is effective in young smokers in a deprived area of Nottingham, UK
Methods and subjects
We surveyed smoking prevalence and attitudes to smoking and quitting in young people accessing an open access youth project in a deprived area of Nottingham, and used the information gained to design a community based smoking cessation service incorporating a randomised controlled trial of nicotine patches against placebo given in association with individual behavioural support. We resurveyed smoking prevalence among project attendees after completing the pilot study.
Of 264 young people surveyed (median age 14 years, range 11–21), 49% were regular smokers. A total of 98 young people were recruited and randomised to receive either active nicotine patches on a six week reducing dose regimen (49 participants), or placebo (49 participants). Adherence to therapy was low, the median duration being one week, and 63 participants did not attend any follow up. At four weeks, five subjects receiving active NRT and two receiving placebo were abstinent, and at 13 weeks none were. Adverse effects were more common in the active group but none were serious. Smoking prevalence among 246 youth project attendees surveyed after the trial was 44%.
This study suggests that NRT in this context is unlikely to be effective in young smokers, not least because of low adherence to therapy. It also suggests that young smokers want help with smoking cessation, but that establishing the efficacy of smoking cessation services for young people who need them most will be very difficult.
nicotine replacement therapy; socioeconomic; youth
To test the efficacy of two smoking cessation interventions in an HIV+ sample: standard care (SC) treatment plus nicotine replacement therapy (NRT) versus more intensive motivationally-enhanced (ME) treatment plus NRT.
randomized controlled trial.
HIV+ smoker referrals from eight Immunology clinics in the Northeastern US.
444 participants enrolled in the study (mean age=42 years; 63% male; 52% European-American; mean cigarettes/day=22.8).
SC received two brief sessions with a Health Educator. Those setting a quit date received self-help quitting materials and NRT. ME received four sessions of motivational counseling and a quit-day counseling call. All ME intervention materials were tailored to the needs of HIV+ individuals.
Biochemically-verified 7-day abstinence rates at 2-month, 4-month, and 6-month follow-ups.
Intent-to-Treat (ITT) abstinence rates at 2-month, 4-month, and 6-month follow-ups were 12%, 9%, and 9% respectively in the ME condition, and 13%, 10%, and 10% respectively in the SC condition, indicating no between-group differences. Among 412 participants with treatment utilization data, 6-month ITT abstinence rates were positively associated with low nicotine dependence (p=0.02), high motivation to quit (p=0.04), and Hispanic-American race/ethnicity (p=0.02). Adjusting for these variables, each additional NRT contact improved the odds of smoking abstinence by a third (OR=1.32, 95% CI= 0.99–1.75).
Motivationally-enhanced treatment plus NRT did not improve cessation rates over and above standard care treatment plus NRT in this HIV+ sample of smokers. Providers offering brief support and encouraging use of nicotine replacement may be able to help HIV+ patients quit smoking.
HIV; tobacco cessation; nicotine replacement; Transtheoretical Model
Effective pharmacotherapies are available for smoking cessation but their efficacy is established through randomised controlled trials where the medication is supplied direct to subjects. In health care settings patient access to medicines is often less direct. The process for obtaining supplies of nicotine replacement therapy (NRT) is relatively easy for smokers attending National Health Service (NHS) Stop Smoking Services in the UK, whilst this is not necessarily the case for those wishing to using prescription only medicines (e.g. bupropion and varenicline). This study was a direct comparison of the short-term validated abstinence rates of NRT and bupropion in a clinical setting.
Data were routinely collected from 2626 clients setting a quit date (82% of those registering) with two London NHS Stop Smoking Services that offered behavioural support combined with pharmacotherapy (NRT and bupropion).
Contrary to what would be expected from multiple randomised controlled trials, the CO-validated 3–4 week abstinence rate in clients using NRT was higher than for bupropion (42% versus 34%, p = .003). This difference persisted even when controlling for smoking characteristics, demographic variables and treatment variables 1.40 (95% CI = 1.08 – 1.83).
Given that the level of behavioural support received by clients on each medication was identical, the most plausible explanation for the difference in effectiveness between NRT and bupropion perhaps lies with how clients of the Stop Smoking Services obtained their medications. Obtaining NRT was relatively easy for clients throughout the study period whilst this was not the case for bupropion. This study suggests that implementation issues and/or self-selection may influence the effectiveness of medications in health care, as opposed to research, settings.
Nicotine replacement therapies (NRT) have been evaluated to facilitate cigarette smoking reduction in smokers unwilling or unable to quit. In most of these studies, only conventional doses of NRT have been tested and higher doses may be required to result in significant reductions in smoking and in biomarkers of exposure.
To determine if higher NRT doses in conjunction with smoking are safe and may promote significant reductions in cigarette smoking and biomarkers of exposure.
A dose-ranging, withinsubject design was implemented to evaluate the effects of 15, 30 and 45 mg nicotine patch treatment on measures of safety and the extent of smoking reduction and biomarker exposure per cigarette in smokers (N = 20 completers) not immediately interested in quitting.
Concurrent smoking and NRT were generally tolerated and resulted in no changes in blood pressure or heart rate. Slightly less than 10% of the study sample was not given the highest dose of NRT due to side effects. Self-reported cigarette smoking decreased with increasing doses of nicotine replacement and significant reductions were observed for total NNAL (a carcinogen biomarker) and carbon monoxide. However, even at the 45 mg dose, increased carbon monoxide and total NNAL per cigarette occurred, even though cotinine levels increased on average, 69.3% from baseline.
The present results suggest that the use of high dose NRT is safe, leads to significant reductions in smoking (-49%), significant but less reductions in total NNAL (-24%) and carbon monoxide (-37%) due to compensatory smoking.
smoking; nicotine replacement; smoking reduction
Nicotine replacement therapies (NRT) are efficacious smoking cessation aids. However, only minimal increases in smoking cessation followed NRT being made available over-the-counter (OTC) which presumably made these treatments more readily available. To better understand why the U.S. did not experience improvements in smoking cessation following the OTC availability of NRT, it is useful to review factors that determine NRT’s impact on smoking cessation and how these factors played out with the introduction of OTC NRT. We contend that for NRT to have a greater impact on public health, we need to increase the number of individuals making a quit attempt, the proportion using NRT in a quit attempt, and the effectiveness of each quit attempt. Even small increases in the impact of OTC NRT could yield significant benefits in terms of morbidity and mortality. The remainder of this paper provides examples of interventions designed to target each of the above mentioned factors individually as well as examples of interventions that link increased cessation attempts, increased NRT reach, and increased NRT efficacy in order to synergistically increase the impact of OTC NRT.
Reducing smoking prevalence is a public health priority that can save more lives and money than almost any other known preventive intervention. Internet interventions have the potential for enormous public health impact given their broad reach and effectiveness. However, most users engage only minimally with even the best designed websites, diminishing their impact due to an insufficient ‘dose’. Two approaches to improve adherence to Internet cessation programs are integrating smokers into an online social network and providing free nicotine replacement therapy (NRT). Active participation in online communities is associated with higher rates of cessation. Integrating smokers into an online social network can increase support and may also increase utilization of cessation tools and NRT. Removing barriers to NRT may increase uptake and adherence, and may also increase use of online cessation tools as smokers look for information and support while quitting. The combination of both strategies may exert the most powerful effects on adherence compared to either strategy alone.
This study compares the efficacy of a smoking cessation website (WEB) alone and in conjunction with free NRT and a social network (SN) protocol designed to integrate participants into the online community. Using a 2 (SN, no SN) x 2 (NRT, no NRT) randomized, controlled factorial design with repeated measures at baseline, 3 months, and 9 months, this study will recruit N = 4,000 new members of an internet cessation program and randomize them to: 1) WEB, 2) WEB + SN, 3) WEB + NRT, or 4) WEB + SN + NRT. Hypotheses are that all interventions will outperform WEB and that WEB + SN + NRT will outperform WEB + NRT and WEB + SN on 30-day point prevalence abstinence at 9 months. Exploratory analyses will examine theory-driven hypotheses about the mediators and moderators of outcome.
Addressing adherence in internet cessation programs is critical and timely to leverage their potential public health impact. This study is innovative in its use of a social network approach to improve behavioral and pharmacological treatment utilization to improve cessation. This approach is significant for reducing tobacco’s devastating disease burden and for optimizing behavior change in other arenas where adherence is just as critical.
Smoking cessation; Internet; Adherence; Social networks; Nicotine replacement therapy
An aversive tobacco abstinence syndrome, thought to reflect an underlying level of nicotine dependence, contributes to cigarette smokers’ failed quit attempts. Nicotine replacement therapy (NRT) suppresses tobacco abstinence, but high relapse rates suggest room for improvement. Improving NRT’s efficacy might begin with identifying factors that influence tobacco abstinence symptom suppression. Two such factors are smokers’ gender and NRT dose. The purpose of this study was to determine the dose-related effects of transdermal nicotine (TN) on tobacco abstinence symptoms in 75 men and 53 women who regularly smoked cigarettes but who had abstained from smoking for at least 8-12 hr. Participants completed 4 double-blind, randomized 6.5-hr laboratory sessions that differed by TN dose (0, 7, 21, or 42 mg). Each session included blood sampling for plasma nicotine level, measurement of heart rate, participants’ ratings of tobacco abstinence symptoms and effects of nicotine, and psychomotor performance. Increases in plasma nicotine level were related to TN dose and were independent of gender. TN-induced abstinence symptom suppression was dose-related for items assessing craving and urge to smoke and largely was independent of gender. TN increased heart rate and ratings of aversive side effects (e.g., nausea, lighthead-edness) in a dose-related manner, and women were more sensitive at higher doses. Results from this laboratory study support the continued use of TN as a pharmacotherapy. Higher doses may ameliorate some abstinence symptoms, although the side effect profile, at least in the short term, may limit effectiveness, especially for women.
nicotine; abstinence; symptoms; gender; dose
Light smoking is particularly prevalent among Latino smokers. Nicotine replacement (NRT) and varenicline are effective medications for smoking cessation for moderate-heavy smokers, but have not been tested in light smokers and thus there are no treatment guidelines for use with light smokers. This pilot trial tested the efficacy of NRT and varenicline in increasing smoking abstinence among Latino light smokers. A 3-group (NRT, varenicline, varenicline-placebo) randomized design was used and Latino light smokers (≤10 cpd) received 12 weeks of treatment which included a culturally-informed behavioral health session and ongoing medication management visits. At follow-up, there were no abstinent participants in the placebo and NRT groups. However, 30% of participants in the varenicline group were abstinent at the 3, 4, and 6 month follow-up. This study represents the only investigation that specifically targets Latino light smokers using these treatments and characterizing their treatment adherence.
Latinos; Hispanics; light smokers; varenicline; adherence; NRT
Tobacco users receiving behavioural and pharmacological assistance are more likely to quit. Although telephone quitlines provide population access to counselling, few offer pharmacotherapy.
To assess change in cessation rates and programme impact after the addition of free nicotine replacement therapy (NRT) to statewide quitline services.
Design, setting, participants
An observational study of cohorts of callers to the Minnesota QUITPLANSM Helpline before (n = 380) and after (n = 373) the addition of access to free NRT.
Mailing of NRT (patch or gum) to callers enrolling in multi‐session counselling.
Main outcome measure
Thirty‐day abstinence six months after programme registration.
The number of callers increased from 155 (SD 75) to 679 (180) per month pre‐NRT to post‐NRT (difference 524, 95% confidence interval (CI) 323 to 725). Post‐NRT, the proportion of callers enrolling in multi‐session counselling (23.4% v 90.1%, difference 66.6%, 95% CI 60.8% to 71.6%) and using pharmacotherapy (46.8% v 86.8%, difference 40.0%, 95% CI 31.3% to 47.9%) increased. Thirty‐day abstinence at six months increased from 10.0% pre‐NRT to 18.2% post‐NRT (difference 8.2%, 95% CI 3.1% to 13.4%). Post‐NRT the average number of new ex‐smokers per month among registrants increased from 15.5 to 123.6 (difference 108.1, 95% CI 61.1 to 155.0). The cost per quit pre‐NRT was $1362 (SD $207). The cost per quit post‐NRT was $1934 ($215) suggesting a possible increase in cost per quit (difference $572, 95% CI −$12 to $1157).
The addition of free NRT to a state quitline is followed by increases in participation and abstinence rates resulting in an eightfold increase in programme impact. These findings support the addition of access to pharmacological therapy as part of state quitline services.
tobacco control; smoking cessation; telephone counselling; nicotine replacement therapy; state programs
Pharmacogenetic smoking cessation interventions would involve smokers being given information about the influence of genes on their behaviour. However, attributing smoking to genetic causes may reduce perceived control over smoking, reducing quit attempt success. This study examines whether attributing smoking to genetic influences is associated with reduced quitting and whether this effect is mediated by perceived control over smoking.
A total of 792 smokers, participating in a trial of nicotine replacement therapy (NRT)-assisted smoking cessation. Participants were informed that the trial investigated relationships between genetic markers and smoking behaviour, but personalized genetic feedback was not provided.
Primary care in Oxfordshire and Buckinghamshire, UK.
Perceived control over smoking and perceived importance of genetic factors in causing smoking assessed pre-quit; abstinence 4, 12, 26 and 52 weeks after the start of treatment.
A total of 515 smokers (65.0%) viewed genetic factors as playing some role in causing their smoking. They had lower perceived control over smoking than smokers who viewed genetic factors as having no role in causing their smoking. Attributing smoking to genetic causes was not associated significantly with a lower probability of quit attempt success.
Attributing smoking to genetic factors was associated with lower levels of perceived control over smoking but not lower quit rates. This suggests that learning of one's genetic predisposition to smoking during a pharmacogenetically tailored smoking cessation intervention may not deter quitting. Further research should examine whether the lack of impact of genetic attributions on quit attempt success is also found in smokers provided with personalized genetic feedback.
Behavioural influences; causal attributions; genetic testing; perceived control; pharmacogenetic intervention; smoking cessation
Underuse of evidence-based treatment for smoking cessation, including use of nicotine replacement therapy (NRT), is widespread, particularly among minority smokers. This paper examines perceptions of NRT among and between racially and ethnically diverse groups of smokers. Nine focus groups were held among homogenous groups of African American, European American, and Hispanic smokers (N = 70). Specific themes included perceptions of: (a) the mechanism by which NRT works; (b) NRT development and regulation (ie, purpose and methods of clinical trials, Food and Drug Administration oversight, etc); (c) efficacy; (d) safety; and (e) overall cost effectiveness. Across all groups, there was a general lack of knowledge of NRT effects and its efficacy, with only moderate knowledge of the mechanism by which NRT works. Concerns about NRT safety were expressed in all groups, with particular apprehension about addictive potential and possible interactions with other medications. Among African American smokers in particular, there was strong suspicion of pharmaceutical industry and government oversight, which coincided with the consensus view that there are too many unknowns about NRT. Among Hispanic smokers, there was less suspicion of NRT but a strong cultural belief in personal responsibility for smoking cessation. Results highlight enduring misperceptions about NRT that likely undermine usage. More education about NRT is needed, not only about its efficacy and safety, but also with regard to its development and regulation. Health care professionals, many of whom are viewed as trustworthy sources of health information, have a particularly important role to promote wider use of proven cessation strategies.
tobacco; minority health; pharmacotherapy
The use of nicotine replacement therapy (NRT) can almost double the chances of success for smokers to quit. Nevertheless, there is still a considerable number of cessation attempts that are made without any treatment. This novel oral formulation, (lozenge containing nicotine bitartrate dihydrate) has been developed to enlarge the offer for efficient smoking cessation drug therapies, assuming that increasing treatment options will bring more smokers to find the support they personally need to stop smoking.
Three pharmacokinetic (PK), one safety and two efficacy studies were carried out with Nicotinell lozenges. PK trials were: (1) a single-dose, three-way crossover study comparing 1 and 2 mg lozenges with 2 mg nicotine gum; (2) a multiple-dose, two-way crossover study comparing 1 mg lozenge with 2 mg gum; (3) a multiple-dose, three-way crossover study comparing 1 and 2 mg lozenges with 4 mg gum. Safety trial: (4) a single dose study to assess the safety of swallowing up to 12 lozenges containing 1 mg nicotine. Efficacy trials: two efficacy studies in (5) France and (6) the USA, including more than 900 smokers followed-up for up to one year, conducted with the 1 mg lozenge.
The results of the individual PK trials showed that the 1 mg Nicotinell lozenge is bioequivalent to 2 mg polacrilex gum, as demonstrated by similar blood PK parameters (tmax, Cmax, AUC). The 2 mg lozenge was found to deliver quantities of nicotine that were intermediate between those delivered by 2 and 4 mg polacrilex gum.
The short-term efficacy of the 1 mg lozenge in comparison with placebo was also demonstrated with significantly more subjects continuously abstinent from smoking with active lozenges on week 6 in two different populations: moderate to heavy smokers (FTND between 4 and 7) OR = 1.72 [95% CI: 1.05–2.80]; heavy to very heavy smokers (FTND 6 and over) OR = 2.87 [95% CI: 1.18–6.97].
Nicotinell lozenges were found to be safe with mainly mild and reversible adverse events. The safety of the 1 mg lozenge formulation, even when misused was also demonstrated.
The data presented in this review demonstrate high nicotine bioavailability, excellent safety profile and proven short-term efficacy of Nicotinell lozenges. At nominal equivalent doses 1 and 2 mg Nicotinell lozenges were shown to deliver larger amounts of bioavailable nicotine compared to the nicotine polacrilex gum. According to the data developed here, the systemic exposure to nicotine could be ranked: 4 mg polacrilex gum > 2 mg Nicotinell lozenge > 1 mg Nicotinell lozenge = 2 mg polacrilex gum.
Adverse events observed during the clinical trials were mild or moderate in severity, transient and completely reversible. With respect to efficacy in smoking cessation, significantly higher continuous abstinence rates were achieved with lozenge compared to placebo. In conclusion, Nicotinell lozenges offer a valuable addition to the therapeutic armamentarium available for smoking cessation.
To determine the association between daily smoking and use of nicotine replacement therapy (NRT), and to determine predictors of greater NRT use among methadone-maintained smokers.
Assignment to free nicotine patch (8 to 12 weeks) plus either (1) a baseline-tailored brief motivational intervention, a quit date behavioral skills counseling session, and a relapse prevention follow-up session (max), or (2) brief advice using NCI's 4 A's model (min).
Five methadone maintenance treatment centers.
Of the 383 methadone-maintained smokers enrolled, 309 (80.6%) set a specific quit date (received NRT) and were located for assessments. Participants were 51.8% male, 78.6% Caucasian, and smoked 26.6 (SD = 12.2) cigarettes/day.
Use of NRT and smoking behaviors during the 180-day follow-up period assessed by the Timeline follow-back method.
On the day following their quit day, 86.4% of participants used NRT. The percentage of participants using NRT was 52.3%, 27.1%, and 10.4% on day 30, day 60, and day 90, respectively. Participants used NRT on 44.1% of the days through the 90 days of the treatment protocol. The estimated odds of smoking abstinence was 7.1 (P < 0.001) times higher on days when NRT was used than on days when NRT was not used, and cigarettes/day was also significantly lower on NRT days (14.93 vs 4.65; P < 0.001).
Nicotine replacement therapy use was inconsistent following an initial quit attempt among methadone-maintained smokers. On days when NRT was used, individuals were likely to smoke at reduced levels or not at all.
methadone maintenance; clinical trial; nicotine replacement; adherence
Objective: To assess differences in demographic and smoking characteristics between smokers who have and have not used nicotine replacement therapy (NRT).
Design: Mail survey of US smokers from a national research panel.
Participants: Smokers 18 years and over who returned a survey on smoking (n = 9630). The sample was weighted to match the US smoker population on age and sex.
Main outcome measures: Compared smokers who had/had not used NRT in a quit attempt (ever NRT use or over the counter (OTC) NRT use) on: demographic characteristics, nicotine dependence, history of craving and withdrawal, expected difficulty quitting, and self reported history of smoking related medical illness and psychopathology.
Results: NRT users (both ever-users and OTC users) were more likely to be older, male, and better educated. They were also heavier smokers, had experienced more craving and withdrawal upon quitting, and scored higher on measures of dependence. These differences were evident among light smokers, and remained even when smoking rate and time to first cigarette were controlled.
Conclusion: Smokers who elect to use NRT differ from non-NRT users in ways that predispose them to failure in cessation. Controlling for smoking rate and time to first cigarette does not eliminate these differences, even among light smokers. These differences must be considered when comparing the effectiveness of NRT among samples of smokers who self select their treatment and are likely to bias such outcome comparisons.
Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts. Smoking cessation counselling provided via telephone can either be reactive (i.e. primarily involving the provision of evidence-based information), or proactive (i.e. primarily involving repeated, sequenced calls from and interaction with trained cessation counsellors). Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation, delivered through the National Health Service (NHS) Smoking Helpline is more effective or cost-effective than reactive support. It will also investigate whether or not providing nicotine replacement therapy (NRT), in addition to telephone counselling, has an adjunctive impact on smoking cessation rates and whether or not this is cost effective.
This will be a parallel group, factorial design RCT, conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow. Participants will be smokers who call the helpline from any location in England and who wish to stop smoking. If 644 participants are recruited to four equally-sized trial groups (total sample size = 2576), the trial will have 90% power for detecting a treatment effect (Odds Ratio) of 1.5 for each of the two interventions: i) proactive versus reactive support and ii) the offer of NRT versus no offer. The primary outcome measure for the study is self-reported, prolonged abstinence from smoking for at least six months following an agreed quit date. A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline.
The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation.
Randomized trials conducted in over-the-counter (OTC) settings have shown that nicotine replacement therapy (NRT) is effective. This paper reviews nonrandomized tests of the effectiveness of OTC NRT.
Literature search via computer and other methods located (a) retrospective cohort studies of users versus nonusers of OTC NRT and (b) studies of quit rates before versus after NRT went OTC or before versus after NRT was given free to quitline callers. The methods were too heterogeneous to allow meta-analysis.
The results were similar for cohort and pre- versus post-studies. Most of the studies found numerically greater quitting among NRT users than nonusers. Often when NRT was not found effective, other assumed effective treatments (e.g., phone counseling) were also not found effective, suggesting biased or insensitive study methods. Only about half of the studies found statistically greater quitting among NRT users, and the most rigorous studies did not find greater quitting among users. Many studies found selection bias, for example, NRT users are more dependent smokers.
Some lines of evidence appear to confirm the effectiveness of OTC NRT, but others do not. We believe further secondary analyses using nonrandomized comparisons are unlikely to resolve this issue due to sensitivity, specificity, and selection bias problems.
To trial an intervention in a real-life setting to motivate low-income smokers to try to quit. The intervention under trial was the addition of subsidised nicotine replacement therapy (NRT) to a standard population quitline service.
Participants were low-income smokers, recruited “cold” via either a letter in the mail or a flyer inserted in a local newspaper. The intervention group received the usual service of multisession counselling from the quitline plus access to heavily subsidised NRT. A comparison group received the usual quitline service only. Participants were followed up at 3, 6, and 12 months. Trial participants were also compared with a sample of general callers to the quitline.
The offer of subsidised NRT recruited more than twice as many low-income smokers than the offer of the cessation service alone (intervention group n = 1000; comparison group n = 377). 63% were first-time callers to the quitline. Intervention respondents showed higher levels of nicotine dependence than comparison group respondents. Comparisons of quitting data were confounded by the differences in the respondents at baseline. 73.5% of smokers in the intervention group tried to quit compared to 61.0% in the comparison group. Unadjusted quit rates were higher in the intervention group than in the comparison group at 3 months and 6 months but not at 12 months.
Disadvantaged smokers were easily engaged to call the quitline, particularly when offered subsidised NRT. Disadvantaged smokers using the quitline, with and without subsidised NRT, achieved cessation outcomes comparable to other studies of “mainstream” smokers.