This study recruited smokers from 19 different cities of the North Central Cancer Treatment Group (NCCTG). The NCCTG is a large cooperative group of oncology practices throughout the USA that performs multiple clinical trials in oncology patients. A total of 1,708 smokers were recruited from the general population, and 1,700 were randomized to the study.
Among these 1,700 smokers, 16 were of Hispanic ethnicity, and 1,684 were non-Hispanic. Of the 1,684 non-Hispanic smokers, 1,512 were white and 172 were minority races (138 were African American and 34 were other races, including Asian-American, American Indian, and Hispanic-American).
This report is a subanalysis of a larger study involving three study phases. The first phase included 12 weeks of open-label medication to measure efficacy; the second phase assessed blinded relapse prevention or blinded re-treatment; finally, a third phase was the post-medication follow-up. Methodology and results of this larger study have been reported previously (Croghan et al. 2007
This current report focuses only on the 1,684 non-Hispanic participants who received the first 12 weeks of medication. Study participants were randomized to receive one of three treatment assignments for 12 weeks: 300 mg of bupropion SR per day (150 mg bid), ad libitum use of a nicotine inhaler (up to 16 cartridges per day), or a combination of both the nicotine inhaler and bupropion. The primary endpoint for the study was the smoking status at the end of the treatment period.
Study entry criteria
Potential subjects were eligible for enrollment if they were at least 18 years of age, had smoked at least ten cigarettes/day for at least 12 months, were motivated to use the study medication according to the study protocol, were in general good health, had the ability to participate in all aspects of the study, and provided written informed consent. Potential subjects were excluded if they were pregnant/breast-feeding, using concurrent behavioral/pharmacologic treatments to stop smoking, using tobacco products other than cigarettes, or taking an investigational drug. Subjects were also excluded if they had a known hypersensitivity/allergy to nicotine, bupropion, or menthol, unstable angina/myocardial infarction, a history of bulimia/anorexia nervosa, seizure disorders, serious head trauma or other predisposing factors to seizure, or chemical dependence on any drug other than nicotine in the past year. Subjects were also excluded if they were using antipsychotics, antidepressants, theophylline, systemic steroids, antiepileptic medications, or a monoamine oxidase inhibitor (MAO-I).
Recruitment and enrollment
Recruitment for this large study included smokers contacting their regional North Central Cancer Treatment Group site and undergoing a telephone pre-screen, consent visit and a screening visit. If the smoker was found to be eligible, they were randomized to one of three medications. After randomization, participants returned for study visits at week 4, week 8, and week 12 post-randomization. The subjects were instructed to abstain from smoking upon awakening on the target quit date. All subjects received the NCI “Clearing the Air” booklet and individual counseling based on the “Smoke Free and Living It” manual© (Mayo Clinic Nicotine Research Program 2000
The National Institutes of Health (NIH) define ethnicity
as the sociological constructs that emphasize the cultural aspect of a group of people, and race
is defined as a biological aspect of a group of people (Crews and Bindon 1991
; O'Neil 2008
). This study uses this definition, which distinguishes between someone’s ethnic origins ("Hispanic origin" and "Not of Hispanic origin") and race (“American Indian or Alaskan Native,” “Asian or Pacific Islander,” “Black or African American,” and “White”) (Executive Office of the President et al. 2007
Severity of nicotine dependence was assessed at baseline using the Fagerström Test of Nicotine Dependence (FTND) (Heatherton et al. 1991
). Scores for this measure can range from 0 to 10, with a score of 6 or higher indicating severe nicotine dependence (Fagerström 1978
). The Health Status Questionnaire (HSQ) (Ware and Sherbourne 1992
) is a 39-item instrument comprised of the original SF-36 items plus three additional items used to screen for depression (Radosevich et al. 1994
). The SF-36 is a global assessment of health concepts that represent basic human values relevant to functional status and well-being (Ware et al. 1993
). Alcohol dependence was assessed using the Self-Administered Alcoholism Screening Test (SAAST) (Hurt et al. 1980
Abstinence from smoking was defined as a self-report of nonsmoking for the previous 7 days and was considered to be biochemically confirmed with an expired air carbon monoxide value below eight parts per million (ppm). If the participant failed either of these two conditions (reported any smoking in the previous 7 days or had a CO greater than 8 ppm) then the participant was categorized as a smoker. In order to produce a conservative estimate of smoking abstinence, study outcome data were analyzed in an intent-to-treat model. If a participant failed to complete a visit for whatever reason (missed a visit or terminated early from the study), the participant was classified as a smoker for that incomplete visit.
Randomization and statistical analysis
Randomization was performed using the Pocok-Simon approach, which is a dynamic allocation procedure that balanced the marginal distributions of the stratification factors between treatment groups (Pocock and Simon 1975
). Stratification factors were: site, gender, number of cigarettes smoked per day (10–39 vs. 40 or more), and number of years smoked (<5, 5–9, >9). Randomization assigned subjects to one of three medications.
Demographics and smoking abstinence rates at 12 weeks were compared using chi-square tests for categorical variables and ANOVA for continuous variables. Comparisons were done between blacks and other minorities to determine if minorities were similar enough to be combined in the main analyses. The main analyses were comparisons between whites and the combined minorities.
The primary endpoint of this study was the week 12, 7-day point-prevalence, biochemically confirmed, smoking abstinence rate. These cessation rates were tested using two-sided chi-squared tests. With about 172 minorities and over 1,500 whites, this study had 80% power to detect a clinically significant 10% point difference in smoking abstinence rates between the two groups (assuming a baseline success rate of 25% for each of the treatments).
Smoking cessation rates at week 12 were modeled using logistic regression. First, bivariate logistic regression models were fit for each explanatory variable. Then stepwise logistic regression models were used to identify variables prognostic for smoking cessation. Variables were added to the model one at a time in a stepwise method with an inclusion significance level of 0.05. Variables included for selection in the logistic models were minority, treatment arm, age, age started smoking, years smoked, gender, education, marital status, number of cigarettes smoked per day, depression status, FTND, body mass index (BMI), previous quit attempts, previous use of nicotine replacement, and the longest duration of smoking abstinence. To assess whether differences between race groups were dependent on treatment, the race-by-treatment interaction effect was added to the final model determined using the stepwise approach.