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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Arch Intern Med. Author manuscript; available in PMC 2010 December 1.
Published in final edited form as:
PMCID: PMC2891174
NIHMSID: NIHMS198078

Comparative Effectiveness of Five Smoking Cessation Pharmacotherapies in Primary Care Clinics

Abstract

Background

Randomized efficacy clinical trials conducted in research settings may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical settings. Effectiveness trials (e.g., in primary care settings) are needed to estimate the benefits of cessation treatments in real-world use.

Methods

1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics. Patients were randomly assigned to five active pharmacotherapies: three monotherapies (Nicotine Patch, Nicotine Lozenge, and Bupropion SR) and two combination therapies (Patch+Lozenge and Bupropion+Lozenge). Patients were referred to a telephone quitline for cessation counseling. Primary outcomes included seven-day point-prevalence abstinence at one week, eight weeks, and six months post-quit, and number of days to relapse.

Results

Among 7128 eligible smokers (≥ 10 cigarettes per day) attending routine primary care appointments, 19% (N=1346) enrolled in the study. Six month abstinence rates were: Bupropion=16.8%; Lozenge=19.9%; Patch=17.7%; Patch+Lozenge=26.9%; and Bupropion+Lozenge=29.9%. Bupropion SR+Lozenge was superior to all of the monotherapies (odds ratios [ORs]: 0.46 to 0.56); Patch+Lozenge was superior to Patch and Bupropion monotherapies (ORs: 0.56 and 0.54, respectively).

Conclusions

One in five smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence-based counseling and medication. In this comparative effectiveness study of five tobacco dependence treatments, combination pharmacotherapy significantly increased abstinence compared to monotherapies. Provision of free cessation medications plus quitline counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit.

Tobacco use continues to be a significant health threat with approximately 438,000 smoking-related deaths occurring annually in the U.S.1 But, substantial progress has been made in the last 40 years in reducing smoking prevalence from 42.4% in 1965 to 20% in 2007.2,3 In part, these declines are the result of the development of effective cessation treatments. For example, meta-analyses of 86 cessation medication studies in the U.S. Public Health Service (PHS) clinical practice guideline Treating Tobacco Use and Dependence: 2008 Update4 (2008 PHS Guideline) confirmed the efficacy of all seven FDA-approved medications as well as nortriptyline, clonidine, and various combination therapies (e.g., Bupropion SR+Nicotine Patch). Yet, most data on cessation pharmacotherapies come from placebo-controlled efficacy trials conducted under ideal circumstance (e.g., with motivated volunteers, inducements for participation, extensive participant contact) with few directly contrasting multiple pharmacotherapies in head-to-head comparisons. Even fewer studies have conducted such head-to-head tests in real-world clinic settings.4

The primary care clinic is an ideal environment in which to study comparative effectiveness of cessation treatments. First, many smokers report being receptive to advice from their primary care provider (PCP) to quit smoking.5 Second, more than 70% of smokers visit their PCP annually.6 Third, health considerations are especially salient in a clinical setting, making patient visits “teachable moments” to intervene with tobacco users and, in addition, a majority of primary care patients who smoke express interest in cessation treatment and many prefer more intensive treatment.7 Finally, primary care-based cessation treatment is cost-effective, even when cessation medications are provided at no cost.8

Clinician intervention with smokers (brief counseling; cessation medication) is recommended by the 2008 PHS Guideline update4 and has been shown to increase the likelihood of successful quitting.4,9 However, PCPs typically have limited time to deliver cessation counseling and clinics often do not have other clinical staff available to provide such services. Telephone tobacco quitlines can serve as “treatment extenders,” by providing cost-effective counseling in conjunction with the initial intervention provided by PCPs.10,11,12 In fact, recent research by Borland and colleagues13 demonstrated that referral of primary care smokers to a quitline (to augment in-clinic treatment) more than doubled cessation rates at one year as compared with the standard in-clinic PCP-based treatment.

The current study was designed to address two primary questions: (1) When smoking cessation medication and counseling are made available at no cost in the primary care setting, what percentage of eligible smokers will make a quit attempt? and, (2) What are the relative short- and long-term abstinence rates of five different smoking cessation pharmacotherapies when used in “real-world” primary care settings? To answer these questions, we recruited 1346 smokers in 12 primary care clinics to participate in a randomized effectiveness trial comparing five cessation pharmacotherapy treatments in combination with phone counseling provided through a state tobacco quitline. The five pharmacotherapy treatments included three FDA-approved monotherapies (Nicotine Patch, Bupropion SR, and Nicotine Lozenge) and two combination therapies (Bupropion+Lozenge, Patch+Lozenge).

The Nicotine Patch was included because it is widely utilized,14 available over-the-counter (OTC), easy to use, and efficacious [odds ratio (OR) =1.9 in the 2000 PHS Guideline].15 Bupropion SR was included because it was found to be efficacious in two large, multicenter clinical trials16,17 at the time of study design and it has been found in some studies to be more efficacious than the Nicotine Patch.17,18 The Nicotine Lozenge was included because it was a relatively new OTC nicotine replacement therapy (NRT), with promising early results (OR=2.0 for 2 mg; OR=2.8 for 4 mg).19

In addition, we tested two combination therapies: Bupropion+Lozenge and Patch+Lozenge. We included Bupropion+Lozenge because we hypothesized that the use of a non-nicotine cessation medication (Bupropion) combined with an ad libitum NRT (Lozenge) would boost cessation rates over those produced by monotherapies. Likewise, we included Patch+Lozenge because the 2000 PHS Guideline15 found that combination NRT was more efficacious than a single NRT.15 Presumably, users of the Patch+Lozenge would have the benefit of steady-state nicotine levels via the patch that could be augmented by lozenge use when urges or cravings to smoke are especially intense. We hypothesized that Patch+Lozenge would boost cessation rates over those produced by monotherapies.

The five pharmacotherapy treatments in the current study were also tested concurrently in a separate placebo-controlled randomized clinical trial (RCT) conducted by our research team as part of the NIH-funded University of Wisconsin Transdisciplinary Tobacco Use Research Center (TTURC) grant. That RCT (reported elsewhere20) randomized 1504 adult smokers (recruited from the community) to the same active medication conditions or placebo; all participants received individual counseling. Results for this efficacy RCT showed that all five active pharmacotherapy conditions were efficacious relative to placebo and that the Patch+Lozenge treatment had the largest OR and was superior to the monotherapies. Although this RCT differed in several ways from the current study (e.g., type of counseling), these two independent studies provide a unique opportunity to assess comparative effectiveness for the same five pharmacotherapy treatments in both an efficacy RCT and a real-world effectiveness environment.

Methods

Participants

Participants were 1346 smokers recruited in 12 Aurora Health Care primary care clinics in Eastern Wisconsin from October 2005 through May 2007. Figure 1 (CONSORT diagram) provides detailed information about study recruitment, enrollment, and follow-up. Primary inclusion criteria included: (1) 18 years of age or older; (2) 10 or more cigarettes per day (CPD) for the past six months; (3) motivated to quit smoking; and (4) if female, willing to use an acceptable contraception while on study medication. Primary exclusion criteria included: (1) history of seizures or convulsions, bipolar disorder, psychosis, bulimia, or anorexia nervosa; (2) head injury requiring hospitalization; (3) myocardial infarction in past month; (4) current use of bupropion or use of an MAO inhibitor in the previous two weeks; (5) blood pressure greater than 160/100; (6) allergy to any of the study medications; (7) serious thoughts of self-harm in the previous two weeks; (8) drug or alcohol dependence in the past six months; and (9) currently pregnant, breast-feeding, or planning to become pregnant within the next three months. This study was approved by the Aurora Health Care Institutional Review Board (IRB) and the University of Wisconsin Health Sciences IRB. Participants received free treatment in exchange for study participation.

Figure 1
CONSORT Diagram

Recruitment and Enrollment Procedures

At each of the 12 clinics, clinic staff (Medical Assistants or MAs, and PCPs) were trained in study recruitment and other related procedures. The role of MAs included screening for tobacco use, advising smokers to quit, assessing willingness to quit smoking, and determining initial study eligibility. MAs also documented each clinical encounter in the electronic health record (EHR) and, for smokers interested in study participation, notified the PCP of the patient's interest, gave the patient the study consent form to review, and faxed a Wisconsin Tobacco Quit Line (WTQL) referral form to the study office. MAs assessed 45,501 patients (see Figure 1); some patients were assessed multiple times (because of separate clinic visits) for a total of 72,435 clinic visits.

Each interested patient was medically evaluated by his or her physician who documented eligibility on a study Medical Clearance Form (MCF) that provided specific exclusionary criteria. For patients meeting inclusion and exclusion criteria, the MCF was faxed to the central study research office. Patients were then called within one business day of their clinic visit by a research assistant who explained the study and obtained verbal informed consent. The research assistant then conducted a study assessment interview, obtained contact information, and faxed information to the WTQL to arrange for phone-based cessation counseling. In addition, the research assistant randomized the patient to treatment, discussed and set a quit date, provided instructions about picking up medication at the clinic pharmacy, faxed a prescription to the clinic pharmacy, and entered the prescription into the EHR. During this same call, the patient was informed which medication he or she would receive.

1504 patients provided provisional consent to participate in the study and were randomized to a medication condition. 1346 of these 1504 patients picked up their study medication at the pharmacy and continued in the study; 158 elected not to pick up their study medication and had no further study participation. At the clinic pharmacy, the pharmacist obtained written consent, dispensed prepackaged study medication, and sent a fax to the central research office verifying that study medication was dispensed to the patient.

Medication Interventions

Participants received free open-label medications. Bupropion SR was up-titrated as per labeling during the pre-quit week to the full dose (150 mg twice daily) and continued for 8 weeks post-quit. The Nicotine Patch was used as follows: the 21 mg patch was used for post-quit weeks 1-4, the 14 mg patch for weeks 5-6, and the 7 mg patch for weeks 7-8. Nicotine Lozenge treatment (4 mg if the first cigarette of the day was smoked within 30 minutes after waking, 2 mg otherwise) consisted of one lozenge every 1-2 hours for the first 6 weeks post-quit, one lozenge every 2-4 hours during weeks 7-9, and one lozenge every 4-8 hours during weeks 10-12. Adverse event (AE) data were not systematically assessed because all medications are FDA-approved and the study was designed to be similar to real-world cessation practice where AEs are not systematically collected. Participants were instructed to contact their PCP for medication-related questions or problems.

Smoking Cessation Counseling

Cessation counseling was provided by the WTQL following fax referral from the study office. WTQL counselors attempted to proactively contact all study participants to conduct an initial assessment to guide the subsequent counseling. Study participants could elect to receive up to four additional counseling calls and could call for additional support if so desired. Cessation counseling elements included those shown to be efficacious in the 2000 PHS Clinical Practice Guideline15 including problem-solving/skills training (e.g., recognition of high-risk situations; improving coping skills) as well as support via encouragement to quit, expression of willingness to help, and reinforcement for progress.

Primary and Secondary Outcomes

Smoking status was assessed during follow-up telephone interviews at 12 and 24 weeks post-quit using a smoking calendar and the time-line follow-back method;21 approximately 75% of patients were successfully contacted for phone follow-ups. Primary post-quit outcomes included seven-day point-prevalence abstinence (0=abstinent, 1=smoking) at one week and eight weeks (based on the week 12 interview), and at six months (based on the 24 week interview). For purposes of survival analysis, the number of days to relapse (defined as latency to smoke on 7 consecutive days after the quit day) in the first six months post-quit (0 to 182 days) was computed. Secondary outcomes included utilization of the WTQL (0=no utilization, 1=at least one call completed) and total minutes of WTQL counseling.

Validity of Self-Reported Smoking Status

While RCT efficacy studies commonly obtain biochemical verification of abstinence at key study endpoints, effectiveness studies such as the current study typically rely only on self-reported abstinence in order to maximize the “real-world” aspect of the study. In addition, collection of biologic samples can be logistically challenging and costly in effectiveness studies. Self-reported abstinence in effectiveness studies has been recommended by the Society for Research on Nicotine & Tobacco (SRNT) Subcommittee on Biochemical Verification,22 and, consistent with this recommendation, biochemical verification of abstinence was not obtained in the current study.

Sample Size

Sample size was based on estimated point-prevalence abstinence rates at six months derived from efficacy meta-analyses15, 23 and relevant effectiveness studies18, 24 available at the time of study design. Power analyses showed that a sample size of 1320 (n=264 per treatment condition) would be adequate to detect differences of at least 13% for six comparisons testing the predicted superiority of the combination medication conditions versus the monotherapy conditions at power=.80 (two-sided tests, Bonferroni-corrected).

Randomization

Smokers were randomized to the five treatment conditions within each clinic with blocking on gender and self-identified race (White/non-White) to ensure the balance of females, males, Whites, and non-Whites allocated to each treatment condition.

Statistical Methods

All comparative analyses were conducted on an intent-to-treat basis: all smokers who were randomized to a treatment and who picked up study medications were included in the analyses; participants with missing data on smoking status were considered to be smoking. Group differences in abstinence rates were tested using multivariate logistic regression with fixed effects for treatment, gender, race (0=non-White; 1=White), and clinic (treated as a fixed effect because the unit of randomization was the patient rather than the clinic). For each of the three study endpoints, six primary group comparisons of point-prevalence abstinence were tested: Bupropion+Lozenge vs. each of the three monotherapies; and, Patch+Lozenge vs. each of the three monotherapies. We also conducted corresponding Cox regression survival analyses of risk of relapse with fixed effects for treatment, clinic, gender, and race included in the model. All tests were two-sided; Bonferroni-corrected p-values were used to control for family-wise error at each endpoint (with six comparisons and an initial α = .05, the Bonferroni-corrected p = .0083). All estimates (e.g., ORs) and 95% confidence intervals were computed using SPSS for Windows Version 16 (SPSS Inc., Chicago, Illinois) or SAS Version 9.1 (SAS Institute Inc., Cary, North Carolina).

Results

Figure 1 shows that 45,501 primary care patients were assessed for study eligibility and that 10,225 were current smokers. Among current smokers, there were 7128 eligible (10+ CPD) smokers (69.7% of all smokers). Of those eligible, 1346 were randomized to treatment, representing approximately 1 in 5 (19%) eligible smokers. Table 1 provides descriptive statistics for sociodemographic and smoking variables for the total sample and by treatment group. There were no statistically significant group differences on any of these variables. Table 2 provides descriptive statistics for selected sociodemographic and smoking variables for each of the 12 primary care clinics. These statistics show that the participating clinics represented a broad range of patient ethnicity, smoking heaviness, employment status, and other characteristics. There were statistically significant clinic differences, as expected given the diversity of patient populations served by the clinics, for all variables (p ≤ .001) in Table 2 except for the Fagerström Test for Nicotine Dependence (FTND)25 score.

Table 1
Descriptive Statistics for Sociodemographic and Smoking History Variables for the Total Sample and by Treatment Group
Table 2
Descriptive Statistics for the Aurora Health Care Primary Care Clinics

Analyses of Primary Abstinence Outcomes

Figure 2 provides seven-day point-prevalence abstinence rates by treatment group at the three post-quit study endpoints. Consistent with study hypotheses, preliminary analyses (with no correction for multiple tests) showed no differences amongst the three monotherapies, or between the two combination therapies, at any of the study endpoints. Thus, subsequent analyses compared each combination therapy with each of the monotherapies as planned. Table 3 provides results for multivariate logistic regression analyses that tested the hypothesis that combination therapies would be superior to monotherapies. As shown in Table 3, with Bonferroni correction, only two combination versus monotherapy comparisons were significant at one week; all Bonferroni-corrected comparisons were statistically significant at eight weeks; and all comparisons except one (Patch+Lozenge vs. Lozenge) were significant at six months. Adjusted ORs for statistically significant (Bonferroni-corrected) comparisons ranged from 0.51 to 0.67 at one week, from 0.44 to 0.47 at eight weeks, and from 0.46 to 0.56 at six months. Without correction for multiple tests, all comparisons (of combination vs. monotherapies) for all three endpoints were statistically significant except for Patch+Lozenge vs. Patch at one week (p=.48) and Patch+Lozenge vs. Lozenge at six months (p=.06).

Figure 2
Abstinence rates at Post-Quit Study Endpoints
Table 3
Combination Cessation Pharmacotherapy Versus Monotherapy Group Comparisons at Study Endpoints, Point-Prevalence Abstinence

A total of 1027 cases (76% of the total sample) had smoking calendar data available for Cox regression survival analyses. The percentage of missing cases did not differ across the five treatment groups [χ2 (df=4; N=1346) = 3.83, p=.430]. Mean days to relapse, Wald values, p-values, and ORs are provided in Table 4. Both combination therapies resulted in lower risk of relapse compared to each of the three monotherapies (Bonferroni-corrected p-values). Figure 3 provides survival curves for the three monotherapies and two combination therapies.

Figure 3
Cox Regression Survival Analysis: Survival Curves
Table 4
Cox Regression Survival Analysis of Days to Relapse for Combination Cessation Pharmacotherapy Versus Monotherapy

WTQL Utilization and Cessation Outcome

Among the 1346 study participants, a total of 545 participants (40.5%) completed at least one WTQL counseling call. There were no statistically significant differences across the five treatment groups in utilization of the WTQL, χ2 (df=4; N=1346) =9.34, P=.053. Utilization rates in the five treatment groups were: 35.5% for Bupropion, 44.4% for Lozenge, 38.7% for Patch, 46.3% for Bupropion+Lozenge, and 37.6% for Patch+Lozenge. Users of the WTQL did not differ from non-users in nicotine dependence (FTND mean for both groups was 5.1), gender, or race, but WTQL users were significantly older (M=45.3 years) than non-users (M=43.7 years), P=.012.

To examine the association between WTQL utilization and cessation outcome, we first computed six month abstinence rates in groups of Quitline users defined by deciles (10 groups) of the total minutes of phone counseling. These results showed that there was not a linear increase in abstinence rates with more minutes of counseling but, instead, users with fewer than 90 minutes of counseling (N=316) had an abstinence rate of 19.6% that was nearly the same as the rate for non-users of the WTQL (N=801; abstinence rate=19.5%). In contrast, WTQL users who had more than 90 minutes of counseling had a six month abstinence rate of 35.8% (P < .001).

Discussion

In this comparative effectiveness study, we found that combination pharmacotherapies for smoking cessation were superior to the three monotherapies, especially at eight weeks and six months. Bupropion+Lozenge combination therapy was especially effective relative to the monotherapies with an approximate doubling of abstinence rates at eight weeks and six months. Similar, though less consistent, results were found for the Patch+Lozenge combination condition. Survival analyses of risk of relapse yielded similar results. These results generally accord well with the findings from the separate RCT efficacy study20 that tested the same five pharmacotherapy treatments. Biochemically-confirmed six month point-prevalence abstinence rates in the efficacy study were: 31.8% for Bupropion, 33.5% for Lozenge, 33.5% for Patch, 33.2% for Bupropion+Lozenge, and 40.1% for Patch+Lozenge.20 In particular, both studies found that the Patch+Lozenge combination therapy was superior to the monotherapies but, unlike the efficacy RCT study, the current effectiveness study also found that the Bupropion+Lozenge combination therapy was superior to the monotherapies. Taken together, these two studies provide independent evidence, consistent with the 2000 and 2008 PHS Guidelines,4,15 that combination cessation pharmacotherapy results in significantly higher long-term abstinence rates in comparison to cessation monotherapies.

The current study expands upon earlier research7 in demonstrating that a substantial proportion of primary care smokers attending routine clinic appointments were willing to make a cessation attempt. Among 7128 eligible smokers, approximately 37% (N=2677) were interested in study participation, 33% (N=2371) passed medical screening, and 19% (N=1346) consented to participation, were randomized to treatment, and picked up study medications. Thus, approximately 1 in 5 primary care patients smoking 10+ CPD were willing to undertake an unplanned quit attempt during a primary care visit that included the opportunity to receive free medication and telephone cessation counseling.

The current study is limited to some extent by the fact that self-reported abstinence was not biochemically confirmed. As such, abstinence rates based on self-report could be over-estimates. However, there is evidence that self-reported abstinence rates are generally accurate in low-contact effectiveness studies.22, 26, 27 It is worth noting that the majority of study participants did not utilize quitline counseling but it is unknown to what extent this lack of broader quitline utilization may have resulted in lower abstinence rates. However, epidemiologic research using 2003 Current Population Survey data on 29,537 U.S. smokers has shown a very low rate (4.1%) of use of counseling (individual, group, and telephone) among smokers making quit attempts.28 Thus, the use of the quitline for counseling by approximately 40% of participants in the current study is encouraging.

The tobacco cessation intervention model used in the current study is consistent with recommendations in the 2008 PHS Guideline4 concerning the use of cessation medications, quitlines, and more intensive counseling. The results confirmed that provision of free medication and easy access to counseling (via a telephone quitline), with both arranged in the primary care setting during a routine (non-cessation related) appointment, can result in a relatively high level of unplanned quit attempts and good cessation success, especially with combination therapy (27% to 30% abstinent at six months). Assuming that 1 in 5 smokers visiting a primary care clinic for routine care will undertake an unplanned quit attempt and that up to 30 out of every 100 of these smokers making a quit attempt could achieve long-term (6-month) cessation, the overall success (defined as long-term abstinence) of this intervention model corresponds to approximately 6 out of every 100 primary care-based smokers (i.e., all smokers including those not motivated to make a quit attempt) achieving long-term abstinence. As such, this model holds significant promise for assisting large numbers of smokers to quit given that tens of millions of smokers are seen each year in the primary care setting.

Additional research is needed on the cost-effectiveness of the interventions in the current study as well as potential future enhancements to this intervention delivery model (e.g., how PCPs can increase smoker motivation to make a quit attempt). However, this comparative effectiveness study identified two particularly effective combination therapies for smoking cessation. These findings provide strong support for the widescale implementation of this efficient primary-care-based intervention model that significantly reduces barriers to patient access to evidence-based cessation treatments.

Acknowledgments

This research was supported by NIH grant 5P50DA019706 (Baker) from the National Institute on Drug Abuse and grant 1K05CA139871 (Baker) from the National Cancer Institute. Dr. Piper was supported by an Institutional Clinical and Translational Science Award (UW-Madison; KL2 Grant # 1KL2RR025012-01). Medication was provided to patients at no cost under a research agreement with GlaxoSmithKline (GSK); no part of this manuscript was written or edited by anyone employed by GSK. The authors are solely responsible for the analyses, content, and writing of this article.

We would also like to acknowledge the contributions of the following organizations and individuals: the Aurora Health Care System; Aurora clinic physicians, medical assistants, and other clinic staff; counselors at the Wisconsin Tobacco Quit Line; staff at Free and Clear, Inc., Seattle, WA; and research staff at the Milwaukee office of the University of Wisconsin Center for Tobacco Research and Intervention (Patti Weston, Sarah Cunitz, Meg Feyen, Leigh Ann Laczkowski, and Michelle Spehr).

Footnotes

Trial Registration: clinicaltrials.gov Identifier: NCT00296647

Financial Disclosure: The authors report the following potential conflicts of interest for the last 5 years. Stevens S. Smith has received research support from Elan Corporation, plc. Douglas E. Jorenby has received research support from Pfizer, Inc., Sanofi-Synthelabo, and Nabi Biopharmaceuticals; he has received consulting fees from Nabi Biopharmaceuticals. Michael C. Fiore has received honoraria from Pfizer. He has served as an investigator on research studies at the University of Wisconsin that were funded by Pfizer, Sanofi-Synthelabo and Nabi Biopharmaceuticals. In 1998, the University of Wisconsin (UW) appointed Dr. Fiore to a named Chair funded by an unrestricted gift to UW from Glaxo Wellcome. Timothy B. Baker has served as an investigator on research projects sponsored by pharmaceutical companies including Sanofi-Synthelabo, Pfizer, Inc. and Nabi Biopharmaceuticals. Drs McCarthy, Christiansen, Piper, and Jackson, and Japuntich, and Mr Fraser have no potential conflicts of interest to disclose. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Contributor Information

Stevens S. Smith, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Danielle E. McCarthy, Department of Psychology, Rutgers, The State University of New Jersey, Piscataway, NJ.

Sandra J. Japuntich, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Bruce Christiansen, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Megan E. Piper, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Douglas E. Jorenby, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

David L. Fraser, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Michael C. Fiore, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Timothy B. Baker, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

Thomas C. Jackson, Department of Medicine and Center for Tobacco Research and Intervention (CTRI), University of Wisconsin School of Medicine and Public Health, Madison, WI.

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