Cost-Effectiveness of Different Combinations of Bupropion SR Dose and Behavioral Treatment for Smoking Cessation: A Societal Perspective

Published Online: March 01, 2004
Harold S. Javitz, PhD; Gary E. Swan, PhD; Susan M. Zbikowski, PhD; Susan J. Curry, PhD; Timothy A. McAfee, MD, MPH; Donna L. Decker, BA; Richard Patterson, MS; and Lisa M. Jack, MA

Objectives: To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release (SR) in combination with behavioral interventions of minimal intensity (tailored mailings [TM]) or moderate intensity (proactive telephone calls [PTC]) for smoking cessation in an actual practice setting. Study Design: Open-label, randomized trial, with 1-year followup, conducted in a large health system based in Seattle, Washington.

Patients and Methods: A total of 1524 adult smokers interested in quitting smoking were randomly assigned to receive 150 mg bupropion SR daily and PTC (n = 382), 150 mg bupropion SR daily and TM (n = 381), 300 mg bupropion SR daily and PTC (n = 383), or 300 mg bupropion SR daily and TM (n = 378). Sufficient medication for 8 weeks of dosing was provided to patients. The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date.

Results: Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM, the additional cost resulted in lower cost effectiveness. The PTC behavioral intervention was more expensive than TM, but the additional effectiveness resulted in almost equivalent cost effectiveness at the 150-mg dose. Costs per additional 12-month nonsmoker (above that expected for placebo) for the 150-mg dose groups averaged $950 and per additional lifetime quitter averaged $1508; for the 300-mg groups these costs were $1342 and $2129, respectively. Cost per life-year and quality-adjusted life-years (QALYs) saved varied substantially by age and treatment, but were no greater than $1100 for all treatment groups when averaged across the age and sex distribution for the study population.

Conclusions: Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments, within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective.

(Am J Manag Care. 2004;10:217-226)

Cigarette smoking has been associated with approximately 440 000 premature deaths in the United States annually during 1995 through 1999.1 Although smoking cessation treatments are more cost effective than many other commonly provided clinical services,2 obtaining the maximal benefits requires identification of cost-effective treatments. Using quit rates from a clinical efficacy trial reported by Jorenby and colleagues,3 Nielsen and Fiore4 compared the costto- benefit ratio of bupropion sustained release (SR) at a dose of 300 mg per day with those of placebo, the nicotine transdermal patch (NTP), and a combination of bupropion SR plus NTP. The primary outcome evaluated was the point-prevalence rate of nonsmoking at 12 months of follow-up, and drug costs were based on the average wholesale price for bupropion SR and the NTP. All treatment arms received the same counseling, which included 9 supportive telephone calls, 9 weekly individual smoking-cessation counseling sessions, and relapse prevention counseling during 4 follow-up clinic visits. Even though intensive counseling was provided, Nielsen and Fiore estimated the midpoint cost for behavioral treatment ($37.50) as if the behavioral intervention consisted of a single brief counseling session with a healthcare provider. (Essentially, Nielsen and Fiore conducted their cost analysis under the assumption that the smoking cessation rates for intensive and brief counseling would be the same.) Including costs for "brief medical counseling," the cost per 12-month nonsmoker for placebo, NTP, bupropion SR, and bupropion SR + NTP groups, were estimated to be $240, $1724, $663, and $1257, respectively.

The purpose of the present study was to examine the issue of cost effectiveness for smoking cessation treatment based on results from a large effectiveness trial of various combinations of bupropion and behavioral counseling in a healthcare setting. We assessed the effects of 2 doses of bupropion SR and 2 behavioral counseling approaches that would be more likely to be used in actual practice than the intense counseling in the Jorenby clinical trial.


Study Design

Data used for the cost-effectiveness analyses were obtained from a field trial of the effectiveness of bupropion SR in an actual practice setting. The trial, conducted at Group Health Cooperative (GHC) in Seattle, Washington, consisted of 4 treatment groups defined by crossing 2 bupropion SR doses (150 and 300 mg per day) with 2 counseling approaches of varying intensity. The more intensive counseling program was the Free & Clear Program, which involved proactive telephone calls (PTC), and the less intensive program was a modified version of the Zyban Advantage Plan program, which relied primarily on tailored mailings (TM). A total of 1524 participants were enrolled and randomly assigned but not blinded to treatment. The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date (not biochemically confirmed). Using an intent-totreat approach, we assigned the status of smoker to the 14.1% of participants who were survey nonrespondents. Details concerning trial methodology and trial outcomes are presented elsewhere.5,6

Population Characteristics

Participants, all members of GHC, were enrolled over a 13-month period between April 1998 and May 1999. GHC is a nonprofit consumer-governed healthcare system, headquartered in Seattle, Washington, serving approximately 600 000 residents of Washington State. The study was advertised in various publications mailed to GHC members and in brochures distributed to GHC clinics. Primary care physicians were informed of the study and were asked to refer eligible patients. A total of 2979 smokers interested in the study underwent detailed telephone screening; 1909 of these recruits were determined to be eligible. Inclusion and exclusion criteria were modeled after a previously conducted bupropion SR efficacy trial3 and focused predominantly on conditions, including use of medications, that may lower seizure threshold. The pretreatment questionnaire and informed consent were obtained from 1524 smokers who were randomized into 1 of 4 treatment groups. Of the 385 smokers who did not end up in the final sample, 323 (84%) did not return their enrollment materials or subsequently refused participation, 23 (6%) were found not to have proper coverage, and the remaining 10% either reported exclusion criteria after screening or were excluded by their personal physician. The final sample of 1524 had an average age of 45.1 years, was 57.4% female, 89.7% white, had 13.7 years of formal schooling, smoked an average of 23.2 cigarettes per day for an average of 26.5 years, and had made 5.9 previous quit attempts. Approximately one-third (30.7%) had previously quit for 6 or more months, and most (63.3%) had previously used nicotine patches or gum.


In the PTC program, all registrants received an outgoing call from a smoking cessation counselor a few days before the estimated quit date. After this call an average of 4 follow-up outgoing calls were made, each taking an average of 11.5 minutes (including time for unsuccessful call attempts), with follow-up letters being sent after 3 unsuccessful attempts to complete a call. Participants could also call an ad hoc support line, with an average usage of 21 minutes per enrollee. In the TM program, the participant was sent an individualized action plan prior to the quit date. On the quit date, the participant received a scripted outgoing call from a customer service representative. At 1, 8, 11, and 24 weeks after the quit date, participants received brief questionnaires that could be completed by mail or by using an automated, interactive voice-response telephone system. Participants who responded to a questionnaire were mailed a tailored relapse prevention/recovery plan. In addition, participants could access an automated tip line or talk to a program specialist; these latter interactions averaged just under a minute (54 seconds) per enrollee.

Cost Estimates

Costs for the various components were estimated (as of January 2003) based on the amount and type of personnel time involved, wage rates and overhead benefits, facilities costs, time spent on indirect tasks related to an ongoing smoking cessation behavioral intervention program (departmental meetings, quality control activities, etc), telephone costs, management costs, printing, and postage. Drug costs were estimated based on contract pricing, pharmacy dispensing costs, and allocable pharmacy overhead. Costs were not included for advertising, training or informing physicians or other medical staff, staff hiring and training, program development costs, materials development costs, or information technology infrastructure investment, because these would be primarily nonrecurring costs. Based on Bureau of Labor Statistics regional employment cost indices for March 2003, differences in regional employment costs could alter the costs of the behavioral intervention by -2.4% (for the South) to +0.6% (for the Midwest).

Cost-effectiveness Calculations

Meta-analyses of smoking cessation studies4,7,8 have shown that control group cessation rates range from 6% to 12%. To adjust for the background quit rates among smokers who are motivated to quit, a 12-month "placebo-adjusted" nonsmoking rate was calculated by subtracting 11% from the observed 12-month nonsmoking rates.

The cost per additional nonsmoker at 12 months was derived by dividing the cost per enrollee by the 12-month placebo-adjusted quit rate. The incremental cost per 12- month quitter for various treatment pairs was also calculated. Previous research9,10 had estimated a 35% to 40% lifetime probability of relapse from smoking cessation after 1 year of abstinence, so lifetime nonsmoking rates were calculated assuming a 37% relapse rate.

The cost effectiveness of the interventions in increasing life expectancy was calculated using the mortality rates given by Croghan and associates.11 The impact of smoking on health-related quality of life was calculated using the Healthy People 2000 years of healthy life measure,9,12 extrapolating the measures down to age 18 years and up to 100 years using piecewise linear extrapolation.

Estimates in the literature for spontaneous quit rates for smokers range from 0.5% to 2.5%.9,10,13-15 Historical estimates for the spontaneous quit rate were used to minimize the portion of spontaneous quits that were aided (ie, through physician counseling, use of prescription or over-the-counter nicotine replacement aids, telephone quit lines, etc). For cost-estimation purposes, we estimated the rate of spontaneous unaided quits followed by a minimum of 12 months of reported nonsmoking to be 1.5%. (However, because this rate may now be higher as a result of increased awareness of the deleterious effects of tobacco, we also examined the effect of increasing the unaided spontaneous quit rate to 2.5% and 3.5%.) Spontaneous quitters who remained nonsmokers for at least 12 months were also subject to later relapse using the 37% relapse rate described above.

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