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© 2003 American Society for Clinical Oncology Nicotine Patch Therapy Based on Smoking Rate Followed by Bupropion for Prevention of Relapse to Smoking
From the Mayo Clinic and Mayo Foundation, Rochester, and Duluth Community Clinical Oncology Program (CCOP), Duluth, MN; Ochsner CCOP, New Orleans, LA; Illinois Oncology Research Association, CCOP, Peoria, IL; Saskatoon Cancer Centre, Saskatoon; Allan Blair Cancer Centre, Regina, Saskatchewan, Canada; Medcenter One Health Systems, and Mid Dakota Clinic, Bismarck, ND; Iowa Oncology Research Association CCOP, Des Moines; Siouxland Hematology-Oncology Associates, Sioux City, IA; Toledo Community Hospital Oncology Program CCOP, Toledo, OH; Geisinger Clinic and Medical Center CCOP, Danville, PA; and Ann Arbor Regional CCOP, Ann Arbor, MI. Address reprint requests to Richard D. Hurt, MD, Mayo Clinic, 200 First St, SW, Rochester, MN 55905; email: rhurt{at}mayo.edu.
Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.
RECENT ADVANCES in pharmacotherapy for smokers have sparked a considerable amount of research to improve treatment alternatives. There now exists a wide array of pharmacologic options for the smoker desiring to stop.1 To date, a consistently effective intervention has not been found to facilitate long-term smoking abstinence in a majority of smokers who stop with pharmacotherapy. Nicotine patch therapy has become a standard treatment for smokers wishing to stop smoking. Studies have shown that, compared with placebo, a doubling of the short- and long-term smoking abstinence rates can be achieved using standard-dose nicotine patch therapy.2,3 Nicotine patch doses up to 63 mg/d have been shown to be safe, but studies of whether higher doses improve efficacy have produced mixed results.4–11 Bupropion has been shown to be an effective pharmacologic adjunct for smokers in a dose response study12 and when compared with nicotine patch therapy.13 More recently, bupropion has been reported to delay relapse to smoking when used for 45 weeks in smokers who were abstinent from smoking after 7 weeks of open-label bupropion treatment.14 Serum nicotine and cotinine concentrations, using standard-dose (21 or 22 mg/d) nicotine patch therapy in abstinent smokers, are about half those found with smoking.2 Although basing the nicotine patch dose on a smoker’s smoking rate has been recommended, it has not been shown whether such a strategy will improve the efficacy of nicotine patch therapy.5 Furthermore, such a strategy has not been studied outside of specialized tobacco research centers. Bupropion has not been tested for pharmacologic relapse prevention after nicotine patch therapy, nor is it known whether bupropion might initiate abstinence in smokers who experienced treatment failure with nicotine patch therapy. This study was designed to answer these questions. The primary goals of this study were to determine whether (1) tailored nicotine patch therapy that is based on smoking rate could be carried out in a multisite oncology investigative group practice setting that had not previously performed smoking intervention trials, (2) long-term use of bupropion will reduce the rate of relapse to smoking compared to placebo in smokers who achieve initial abstinence from smoking with nicotine patch doses matched to baseline smoking rates, and (3) bupropion can initiate abstinence among smokers who failed to stop smoking after 8 weeks of nicotine patch therapy. An ancillary goal was to assess toxicities associated with this combined treatment approach.
The North Central Cancer Treatment Group (NCCTG) is a large cooperative group of oncology practices that performs multiple clinical trials each year in oncology patients. Mayo Clinic Rochester serves as the coordinating center. The investigative sites are not specialized in smoking intervention trials; thus, these results may be more reflective of real-world efficacy for smoking abstinence rates after pharmacotherapy. Fourteen sites within the NCCTG (excluding Mayo Clinic Rochester) participated in this study. Institutional review board approval was obtained independently by each site after the study protocol was reviewed. Participants were not cancer patients; rather, they were recruited from the general population of smokers at each NCCTG site in a variety of ways (press releases to media, advertisements, word of mouth, clinic flyers, and so on). Individual sites may have used one or more of the recruitment strategies. Prospective participants were asked to phone the study sites, at which time a telephone screen was used to determine their eligibility. Inclusion criteria included being  18 years of age, being in general good health, smoking 15 cigarettes per day (cpd) for the past year, and having a negative pregnancy test at entry for females of childbearing potential. Exclusion criteria included recent (< 3 months) myocardial infarction; current ( 1 month) major psychiatric disorder or use of major psychiatric medications; pregnancy or breast feeding; current use of nicotine replacement therapy, bupropion, clonidine, or other medications known to help a smoker stop; previous use of bupropion; current use of tobacco products other than cigarettes; active alcoholism or drug dependence; history of serious head trauma; history of or predisposition to seizures; or past history of anorexia or bulimia.
Those who met the initial criteria were invited to attend an information meeting wherein details of the study were discussed and final eligibility was determined. Figure 1
After enrollment, an 8-week treatment with nicotine patch therapy was initiated. Nicotine patch dosage was based on smoking rates reported at the time of the telephone screening. Those smoking 20 cpd were assigned to the 22 mg/d nicotine patch dose, those smoking 21 to 40 cpd were assigned to the 33 mg/d nicotine patch dose, and those smoking more than 40 cpd were assigned to the 44 mg/d nicotine patch dose. This was based on a previously reported algorithm that was determined using plasma cotinine concentrations and calculated percentage nicotine replacement.5 Treatment assignment was carried out using a dynamic allocation procedure that balances the marginal distributions of the stratification factors among the treatment groups.18 Stratification factors used were sex, the reported number of cigarettes smoked per day (15 to 39 v 40), and total years of smoking (< 5 years v 5 to 9 years v 10 or more years). Dose modification after the initial treatment related to toxicity or treatment success was at the discretion of the investigator. Participants were provided a brief message to stop smoking by a healthcare provider and were given the National Cancer Institute self-help booklet, Clearing the Air. Participants were required to return after 4 and 8 weeks to assess compliance, toxicity, and smoking status. Compliance to nicotine patch use was by self-report. Self-reported abstinence from smoking for the previous 7 days was considered to be biochemically confirmed with an expired air CO of less than 8 ppm. On completion of the nicotine patch therapy, participants were eligible to be randomly assigned to one of two treatment arms depending on their smoking status during week 8. Participants who reported being abstinent from smoking during week 8 and who had an expired air CO of less than 8 ppm were invited to be randomly assigned to receive 6 months of relapse prevention pharmacotherapy with bupropion or placebo, beginning with 150 mg/d for 3 days, then 150 mg bid. Participants were asked to return monthly for the 6 months of the relapse prevention medication phase, then at 9 and 12 months. Self-reported smoking status and expired air CO were collected at each visit. Medication compliance was by self-report. Dose modifications for both of these arms were at the discretion of the physician investigator at each site. Those participants self-reporting smoking during week 8 were invited to be randomly assigned to receive 8 weeks of treatment with bupropion or placebo. The bupropion and placebo treatment doses were 150 mg daily for 3 days followed by 150 mg bid. Participants were asked to return monthly after beginning bupropion therapy through 6 months postassignment. Self-reported smoking status and expired air CO were collected at each visit. Medication compliance was by self-report. The relapse prevention phase of the study was conducted as a randomized, double-blind, placebo-controlled clinical trial after open-label nicotine patch therapy. The primary end point for the relapse-prevention portion of the study was the 6-month point prevalence smoking abstinence rate. For the portion of the trial in which bupropion or placebo was administered to subjects who failed to stop smoking using nicotine patch therapy, the primary end point was the week 8 point prevalence smoking abstinence rate. Point prevalence was defined as no smoking in the previous 7 days. Self-reported smoking abstinence was considered to be biochemically confirmed by an expired air CO of less than 8 ppm. If either one of the variables indicated smoking, then the participant was classified as a smoker (intent-to-treat analysis). Furthermore, those who missed a visit were counted as a treatment failure (ie, classified as a smoker using an intent-to-treat analysis). Treatment evaluations were performed at baseline, monthly for the first 6 months, and at 9 and 12 months postassignment for those subjects who were not smoking at the end of nicotine patch therapy. Included in each treatment evaluation was an update of medical history and an additional administration of the Health Status Questionnaire. Toxicities previously documented as being related to the study treatments were recorded at each treatment evaluation and included any report of nausea, vomiting, constipation, headache, seizures, anxiety, dermatitis, dizziness, dry mouth, insomnia, mental confusion, nervousness, rash, and sweating. All toxicities were graded per National Cancer Institute Common Toxicity Criteria classifications.19 Participants who failed to keep an appointment following random assignment were contacted and rescheduled for another appointment, ideally within 7 days of the original appointment. If an entire assessment was missed, the participant was classified as a smoker in an intent-to-treat fashion. Similarly, if a patient was lost to follow-up, they were classified as a smoker. This produces conservative estimates of smoking abstinence but allows for treatment outcomes that are based on the entire sample.
Statistical Considerations
The primary end point for the nicotine patch treatment phase (arm A in Fig 1
The primary end point for the relapse prevention portion of the trial (arms D and E in Fig 1
The primary end point for the second-line smoking intervention portion of the trial (arms B and C in Fig 1 The number of subjects who ultimately became available for the second random assignment was considerably smaller than was anticipated (370 as opposed to the planned 540 subjects). This leaves us with less power than the original design specifications for the relapse prevention and second-line smoking intervention portions of the trial. With roughly 90 subjects per arm for both second randomization analyses, there was roughly 80% power to detect differences of 13% in the relapse rates (instead of the planned 10%) and 20% in the abstinence rates (instead of the planned 17%) for the relapse prevention and second-line prevention portions of the study, respectively. Hence, despite the reduced sample size, the study was adequately powered to detect reasonable effect sizes. Secondary end points regarding long-term abstinence and relapse rates for both the second-line intervention and relapse prevention portions of the study were collected monthly after the treatment periods in each phase had been completed. The statistical methods and power considerations for these end points were the same as those for the primary end points. Secondary end points of toxicity prevalence were compared in a manner similar to that for the primary end point using the same equality of binomial proportions procedures. Toxicity grade distributions were compared across treatment arms using Wilcoxon rank sum testing.21
Balance in the baseline characteristics across treatment arms was carried out via
A total of 583 participants were initially enrolled from the 14 NCCTG institutions. Three participants canceled before starting treatment, and two others were subsequently found to not meet inclusion-exclusion criteria. Thus, the final sample consisted of 578 subjects. Of the 578 subjects initially enrolled, 66% completed the 8 weeks of nicotine patch therapy. The other subjects dropped out primarily because they never attained initial abstinence from, or relapsing to, smoking. Baseline characteristics for the participants are shown in Table 1  .
Table 2 shows the mean smoking rates in the three nicotine patch dose assignments along with the point prevalence smoking abstinence rates for the first and second month of nicotine patch therapy (month 2 was the end of nicotine patch treatment). Overall, 31% of participants were abstinent from smoking at the end of nicotine patch therapy (month 2). On the basis of their baseline smoking rates, 49% of the participants were assigned to the 22 mg/d patch dose, 41% were assigned to the 33 mg/d patch dose, and 10% were assigned to the 44 mg/d patch dose. Thus, we did not achieve the projected even distribution among the three nicotine patch doses. The smoking abstinence rate for the 22 mg/d patch was higher than that for the other two patch doses, but not statistically so (P = .11). For the most part, the dosing guidelines were followed by the treating providers. We checked the baseline smoking rates in cigarettes per day versus the initial nicotine patch dose and found some variance from what we would have predicted. There were a total of 30 subjects who were assigned to an incorrect patch dose, given their reported baseline smoking rate. There was some confusion on the part of the study sites in initial dosing because the subjects reported changed smoking rates from the telephone screen to the time of the first clinic visit. The protocol called for subjects to have the nicotine patch dose that was based on the smoking rate at the time of the telephone screen. Those smoking 20 cpd were to receive a 22 mg/d patch dose, those smoking 21 to 40 cpd were to receive 33 mg/d, and those smoking more than 40 cpd were to receive a 44 mg/d dose. There were seven subjects assigned to the 22 mg/d nicotine patch dose who should have received 33 mg/d, six subjects assigned to the 33 mg/d dose who should have received 22 mg/d, one subject assigned to the 33 mg/d dose who should have received 44 mg/d, 15 subjects assigned to the 44 mg/d dose who should have received 33 mg/d, and one subject assigned to the 44 mg/d dose who should have received 22 mg/d.
Table 3 displays the 7-day point prevalence smoking abstinence rates for the subjects who were assigned to the relapse prevention arm (arms D and E in Fig 1 ). The median time to smoking relapse from random assignment was 2 months for both the placebo and bupropion groups. The percentage of participants who relapsed over time was basically the same whether or not they received bupropion. The primary end point at the end of the bupropion relapse prevention phase indicates a smoking abstinence rate of 28% (95% confidence interval [CI], 19% to 39%) versus 25% (95% CI, 16% to 35%) for bupropion and placebo, respectively (P = .73). Figure 2 shows the percentage of subjects who were abstinent from smoking after completing the nicotine patch therapy and were randomly assigned to bupropion or placebo for 6 months and followed for an additional 6 months.
The differential in successful smoking abstinence was minimal among the minority participants compared to nonminorities. At the end of nicotine patch treatment, 25% (95% CI, 16% to 37%) of minorities were abstinent from smoking compared with 29% (95% CI, 25% to 34%) of their white counterparts. For those who were not smoking at the end of nicotine patch therapy and who were randomly assigned to the relapse-prevention arm, 25% (95% CI, 5% to 57%) of minorities compared with 29% (95% CI, 19% to 40%) of whites were abstinent from smoking at the end of bupropion treatment.
During the nicotine patch phase, mild skin reactions were the most common adverse symptom reported. Of the 208 subjects who dropped out before potential random assignment to placebo or bupropion, only five (2%) dropped out because of adverse events. Table 4
For the subjects who were not smoking at the end of nicotine patch therapy, 176 of the 181 who were eligible (97%) were randomly assigned to placebo or bupropion; 50%, 39%, and 32% completed the protocol through to the 6-, 9-, and 12-month time point evaluations, respectively. Of the subjects still smoking after nicotine patch therapy, only 29% completed the protocol through 6 months.
For those who were still smoking after completing the nicotine patch therapy, 194 of the 397 who were eligible (49%) were randomly assigned to bupropion or placebo. The end of bupropion treatment (8 weeks of medication) abstinence rates were 3.1% (95% CI, 1% to 19%) and 0.0% (95% CI, 0% to 4%) for the bupropion group and for placebo (P = .12). Figure 3
This is the first study in which nicotine patch doses were tailored on the basis of the participant’s smoking rate and in which up to twice the standard nicotine patch dose was used. Furthermore, this study demonstrates the capability of providing nicotine patch therapy with a dose that is higher than the standard outside of specialized nicotine-dependence treatment clinics; it was successfully carried out in a multisite oncology investigative group practice setting. In addition, it is the first study to use bupropion for relapse prevention after initial smoking abstinence was achieved with nicotine patch therapy. It is also the first study to provide immediate retreatment with bupropion or placebo for smokers who experienced treatment failure with initial nicotine patch therapy. Although the abstinence rate at the end of nicotine patch therapy seemed to be higher in those receiving the 22 mg/d dose, the mean baseline smoking rate for those receiving 44 mg/d of nicotine patch was more than 2.5 times that of those assigned to the 22 mg/d patch (47.5 ± 11.6 v 18.8 ± 3.6 cpd). Thus, those subjects assigned to the higher patch dose were likely substantially underdosed.5 The success rate can only be speculated had the heavier smokers been assigned to a single patch dose (22 mg/d), but it is not outside the realm of reason to believe that the success rate would have been much lower than the 21% to 28% experienced in those receiving the 44 mg/d dose. Even those receiving the intermediate dose (33 mg/d) had a significantly higher baseline smoking rate than those assigned to the 22 mg/d dose (30.1 ± 6.0 v 18.8 ± 3.6 cpd). A limitation to these observations is the absence of serum nicotine or cotinine concentration to estimate the percentage of nicotine replacement. On the basis of our previous work, those assigned to the 22 mg/d doses were likely more adequately replaced than the much heavier smokers assigned to the 44 mg/d dose.5 Although lower than our projected smoking abstinence rate of 50% at the end of nicotine patch therapy, the point prevalence smoking abstinence rate we observed was higher than would be expected on the basis of the US Public Health Service guideline.3 The lower than expected smoking abstinence rate in those assigned to the 22 mg/d dose may be due to the more intensive screening performed at sites specializing in smoking intervention trials, the weekly versus monthly visit schedule, the study setting (specialized versus real world), or the experience of the investigative team.2 Most randomized clinical trials performed in the setting of experienced tobacco researchers provide for weekly visits during the treatment phase and monthly visits during the relapse prevention phase.2,14 The smoking abstinence rates we report are considered conservative because with an intent-to-treat analysis, subjects who miss a visit or who are lost to follow-up are considered to have experienced treatment failure (ie, smoking). We also did not find any treatment benefit for bupropion therapy for those who experienced treatment failure with initial nicotine patch therapy. Although this is the first time this sequence has been tested, the results are consistent with the existing literature that shows that retreatment relatively soon after initial treatment with pharmacotherapy does not seem to be of great benefit in initiating smoking abstinence.25 In these participants, there was a substantial reduction in smoking rate during bupropion or placebo treatment, but within a few months, the smoking rate had returned to baseline levels. In addition, smoking abstinence rates at the end of nicotine patch therapy were not different in whites compared with minority smokers. In this study, we found that sustained-release bupropion was not effective in delaying relapse to smoking following initial smoking abstinence after tailored nicotine patch therapy. This is in contrast to the only other reported pharmacologic relapse prevention study, in which we showed that sustained-release bupropion was effective in delaying the time to first relapse following initial smoking abstinence using bupropion.14 In that study, point prevalence smoking abstinence rates were significantly higher in the bupropion group compared with the placebo group during the treatment period and for 6 months following treatment. In the present study, there was virtually no difference between the time to relapse between the bupropion and placebo groups, and the 6-month postassignment smoking abstinence rates were basically identical in the two groups. Furthermore, there were no differences on the basis of race, but the minority sample randomly assigned to bupropion or placebo for relapse prevention was small. The outcomes of the two studies differ for a variety of reasons. In this study, the participating sites were not specialized sites that regularly perform smoking intervention trials. Furthermore, there were fewer and less frequent follow-up visits for the study subjects in this study. In addition, not only was the behavioral counseling less frequent, it was also less intensive. These factors are important to future research because the conditions under which smokers in this study received treatment probably are closer to what the current clinical environment can provide. Nonetheless, it was a randomized, placebo-controlled trial, which by design should have overcome some of those differences if there had been a substantial medication effect. Another major difference was that this bupropion treatment phase lasted for 6 months postassignment, whereas the duration of double-blind bupropion treatment in the other trial was 12 months.14 Nonetheless, most of the relapse occurred early, so that an additional 6 months of treatment in this study would probably have made little difference. Furthermore, the initial abstinence rate (after nicotine patch therapy) was substantially lower than that seen after open-label bupropion treatment in the other relapse prevention trial. This might indicate a lower level of motivation of the subjects involved in this trial and, thus, could have had an effect on long-term outcomes. Finally, we did not have an independent check (such as serum bupropion concentrations) for medication compliance. Noncompliance to taking the active medication could have affected the overall efficacy. We found that both tailored-dose nicotine patch therapy and bupropion were well tolerated. Side effects for the nicotine patch therapy were limited mainly to mild skin eruptions, whereas for bupropion, there was no difference between active medication and placebo in reported adverse events. Specifically, there were no seizures reported, but we did screen out subjects who had a past history of seizures, serious head trauma, or anorexia or bulimia from entry into the study.
Supported by the National Cancer Institute through the North Central Cancer Treatment Group. Supported in part by Public Health Service grants CA-25224, CA-37404, CA-15083, CA-63826, CA-35272, CA-35113, CA-35101, CA-35103, CA-35415, CA-35448, CA-63848, CA-52352, CA-35195, and CA-35103. Medication was supplied by Glaxo Wellcome (Research Triangle Park, NC) and Elan Pharmaceutical (Athlone, Ireland). Additional participating institutions include: CentraCare Clinic, St. Cloud, MN (Harold E. Windschitl); Cedar Rapids Oncology Project CCOP, Cedar Rapids, IA (Martin Wiesenfeld); Mayo Clinic and Mayo Foundation, Rochester, MN (Jan C. Buckner); Carle Cancer Center CCOP, Urbana, IL (Kendrith M. Rowland); and Sioux Community Cancer Consortium, Sioux Falls, SD (Loren K. Tschetter).
1. Hughes JR, Goldstein MG, Hurt RD, et al: Recent advances in the pharmacotherapy of smoking. J Am Med Assoc 281:72–76, 1999
2. Hurt RD, Dale LC, Fredrickson PA, et al: Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up—One-year outcome and percentage nicotine replacement. J Am Med Assoc 271:595–600, 1994 3. Fiore MC, Bailey WC, Cohen SJ, et al: Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD, US Department of Health and Human Services, Public Health Service, 2000 4. Fredrickson PA, Hurt RD, Lee GM, et al: Safety and tolerability of high dose transdermal nicotine therapy for heavy smokers. Psychopharmacology 122:215–222, 1995[CrossRef][Medline]
5. Dale LC, Hurt RD, Offord KP, et al: High-dose nicotine patch therapy: Percentage of replacement and smoking cessation. J Am Med Assoc 274:1353–1358, 1995 6. Hughes JR, Lesmes GR, Hatsukami DK, et al: Are higher doses of nicotine replacement more effective for smoking cessation? Nicotine Tob Res 1:169–174, 1999[Abstract] 7. Zevin S, Jacob P, Benowitz NL: Dose-related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther 64:87–95, 1998[CrossRef][Medline] 8. Killen JD, Fortmann SP, Davis L, et al: Do heavy smokers benefit from higher dose nicotine patch therapy? Exp Clin Psychopharmacol 7:226–233, 1999[CrossRef][Medline]
9. Jorenby DE, Smith SS, Fiore MC, et al: Varying nicotine patch dose and type of smoking cessation counseling. J Am Med Assoc 274:1347–1352, 1995
10. Hughes JR: Treatment of nicotine dependence. Is more better? J Am Med Assoc 274:1390–1391, 1995 11. Tønnesen P, Paoletti P, Gustavsson G, et al: Higher dosage nicotine patches increase one-year smoking cessation rates: Results from the European CEASE trial. Eur Respir J 13:238–246, 1999[Abstract]
12. Hurt RD, Sachs DPL, Glover ED, et al: A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337:1195–1202, 1997
13. Jorenby DE, Leischow SJ, Nides M, et al: A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340:685–691, 1999
14. Hays JT, Hurt RD, Rigotti NA, et al: Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. Ann Intern Med 135:423–433, 2001 15. Heatherton TF, Kozlowski LT, Frecker RC, et al: The Fagerström test for nicotine dependence: A revision of the Fagerström Tolerance Questionnaire. Br J Addict 86:1119–1127, 1991[CrossRef][Medline] 16. Ware JE, Sherbourne CD: The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36): Conceptual framework and item selection. Med Care 30:473–483, 1992[Medline] 17. Swenson WM, Morse RM: The use of a Self-Administered Alcoholism Screening Test (SAAST) in a medical center. Mayo Clin Proc 50:204–208, 1975[Medline] 18. Pocock SR, Simon R: Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 31:103–115, 1975[CrossRef][Medline] 19. Croghan GA, Sloan JA, Croghan IT, et al: Comparison of a 15 mg/16 hour nicotine patch alone versus nicotine nasal spray alone versus both for treating smokers: A randomized multicenter trial in a community practice setting. Nicotine Tob Res (in press) 20. Cohen J: Statistical Power Analysis for the Behavioral Sciences. Hillsdale, NJ, Lawrence Erlbaum, 1988 21. Moses L, Emerson J, Hosseini H: Analyzing data from ordered categories. N Engl J Med 311:442–448, 1984[Abstract] 22. McCullagh P, Nelder JA: Generalized Linear Models. Chapman and Hall Ltd, New York, 1983 23. Agresti A: Categorical Data Analysis. John Wiley and Sons, New York, 1990 24. Moses LE, Emerson JD, Hosseini H: Analyzing data from ordered categories. N Engl J Med 311:442–448, 1984[Abstract] 25. Tønnesen P, Norregaard J, Sawe U, et al: Recycling with nicotine patches in smoking cessation. Addiction 88:533–539, 1993[CrossRef][Medline] Submitted August 27, 2001; accepted November 1, 2002.
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 testing. If pairs of dose level abstinence rates are truly more than 15% apart, we had more than 80% power to detect such an effect, assuming a relatively uniform patch dose distribution (ie, roughly 180 smokers per dose level), a two-sided alternative, and a 5% type I error rate for a test of equality for binomial proportions.
