Smoking, Smoking Cessation
Conditions
Keywords
Smoking, Smoking cessation, Medication adherence
Brief summary
Research shows that smoking cessation is the most significant preventable health behavior change that a person can make to lower cancer risk. In addition, telephone quitlines are an effective, science-based smoking cessation treatment that is universally accessible to smokers in the U.S. However, little research has explored promising approaches that could increase quitline use, improve quit rates, and inform resource allocation for quitline services. The proposed study will test three promising enhancements to the standard quitline treatment that typically consists of counseling and, possibly 2 weeks of a NRT medication. These enhancements are: 1) combination nicotine replacement therapy as recommended by the United States Public Health Service Clinical Practice Guideline on Treating Tobacco Use and Dependence; 2) extended duration of cessation medication use; and 3) an innovative counseling addition - cognitive medication adherence counseling - to optimize adherence to cessation medication. In addition, the cost-effectiveness of each intervention will be calculated. The findings of the proposed research have broad potential application and relevance to state quitlines, quitline service providers, and other purchasers of quitline services such as employers and insurers. Additionally, the study findings can potentially inform other telephone health behavior counseling programs.
Detailed description
The study design is a fully crossed 2x2x2 factorial design that tested the effect of two versus six weeks of nicotine replacement therapy (NRT), the effect of NRT monotherapy (nicotine patch alone) versus NRT combination therapy (nicotine patch + oral NRT), and the effect of cognitive medication adherence counseling (CMAC) versus no CMAC. A total of 987 smokers seeking cessation assistance from the Wisconsin Tobacco Quit Line (WTQL) were randomly assigned to the eight (2x2x2) different conditions generated by the three experimental factors. This design provides us with sufficient power to analyze each of our three main effects listed above. We will also test for two- and three-way interactions, but do not have sufficient data to make a priori assumptions about interaction effects. Finally, we will conduct a cost-effectiveness analysis for each of the three interventions to allow readers of this research to evaluate whether the additional costs of the interventions yield sufficient gains to warrant implementing them broadly.
Interventions
DRUGNicotine patch
If \> 10 cigs/day: one 21 mg nicotine patch per day If \< or = 10 cigs/day: one 14 mg nicotine patch per day
DRUGNicotine gum
If \< 25 cigs/day, 2 mg nicotine gum, at least 5 pieces of oral NRT per day (maximum of 1 piece every 1-2 hours), unless this amount of use produces nicotine toxicity effects. If ≥ 25 cigs/day, 4 mg nicotine gum, at least 5 pieces of oral NRT per day (maximum of 1 piece every 1-2 hours), unless this amount of use produces nicotine toxicity effects.
BEHAVIORALCMAC
CMAC consists of tailored cessation counseling to improve medication adherence during the counseling calls. The CMAC protocol was developed by study investigators and involved: (1) pre-quit assessment of beliefs that might undermine NRT adherence; (2) on-going medication adherence assessment by quitline Quit Coaches; and (3) tailored coaching based on the ongoing assessments.
Sponsors
Wisconsin Department of Health and Family Services
Consumer Wellness Solutions
Department of Health and Human Services
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The only people eligible for this study are Wisconsin residents who contact the Wisconsin Tobacco Quit Line for smoking cessation services. Inclusion Criteria: * Callers will be eligible to participate in the study if they are English speaking; are 18 years of age or older; smoke a minimum of 10 cigarettes per day; are interested in quitting and are willing to set a quit date; willing and able to use nicotine patch and nicotine gum; agree to receive four follow-up counseling calls from Free & Clear (the quitline vendor for the State of Wisconsin); provide verbal informed consent; and provide contact information and agree to take four study follow-up calls from staff at the University of Wisconsin Center for Tobacco Research and Intervention.
Exclusion criteria
* Callers will be excluded if they are under the age of 18; are pregnant or breastfeeding; exclusively use other forms of tobacco (e.g., smokeless tobacco); are unwilling or unable to use study NRT medications; are currently using a cessation medication (NRT, bupropion, varenicline); or have medical exclusions as per FDA-approved product labeling.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 7-Day Point Prevalence Abstinence From Smoking by Intervention | 26 weeks after the target quit smoking date | Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day. |
| 7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group | 26 weeks after the target quit smoking date | Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group | 26 weeks after the target quit smoking date | For cost analyses, we computed the costs of intervention per caller, the cost per quit based on the 6-month ITT 7-day PPA, and the incremental cost-effectiveness ratio (ICER. Intervention costs included direct costs associated with registration, provision of NRT and counseling (standard and MAC), and mailing of a quit guide (all participants) and a MAC information sheet (MAC participants only). Facility space, supplies, and physician supervision time were included in the call costs; research-related costs were excluded. ICER ratio is a measure of the added cost per added quit for two treatments. ICER was computed as the cost difference between the least intensive treatment group (2 weeks of nicotine patch only) and a more intensive comparison group divided by the difference in the quit rates of the two groups being compared; e.g., the ICER for the group that received 2 weeks of nicotine patch and nicotine gum = (213-178)/(.482-.384) = $357. |
Countries
United States
Participant flow
Recruitment details
Adult smokers who called the Wisconsin Tobacco Quit Line (WTQL) from April 1, 2010 to June 15, 2010 were invited to participate in the study; no advertising or targeted recruitment was utilized.
Participants by arm
| Arm | Count |
|---|---|
| 2 Weeks of Nicotine Patch Only, No CMAC Participants in this randomization group received 2 weeks of nicotine patch only and standard quitline cessation counseling consisting of 4 proactive counseling calls (but no Cognitive Medication Adherence Counseling (CMAC). | 119 |
| 2 Weeks of Nicotine Patch Only Plus CMAC Participants in this randomization group received 2 weeks of nicotine patch only and standard quitline cessation counseling consisting of 4 proactive counseling calls plus Cognitive Medication Adherence Counseling (CMAC). | 126 |
| 2 Weeks of Nicotine Patch+Nicotine Gum , No CMAC Participants in this randomization group received 2 weeks of nicotine patch plus nicotine gum and standard quitline cessation counseling consisting of 4 proactive counseling calls (but no Cognitive Medication Adherence Counseling (CMAC). | 123 |
| 2 Weeks of Nicotine Patch+Nicotine Gum and CMAC Participants in this randomization group received 2 weeks of nicotine patch plus nicotine gum and standard quitline cessation counseling consisting of 4 proactive counseling calls plus Cognitive Medication Adherence Counseling (CMAC). | 122 |
| 6 Weeks of Nicotine Patch Only, No CMAC Participants in this randomization group received 6 weeks of nicotine patch only and standard quitline cessation counseling consisting of 4 proactive counseling calls (but no Cognitive Medication Adherence Counseling (CMAC). | 122 |
| 6 Weeks of Nicotine Patch Only Plus CMAC Participants in this randomization group received 6 weeks of nicotine patch only and standard quitline cessation counseling consisting of 4 proactive counseling calls plus Cognitive Medication Adherence Counseling (CMAC). | 127 |
| 6 Weeks of Nicotine Patch+Nicotine Gum , No CMAC Participants in this randomization group received 6 weeks of nicotine patch plus nicotine gum and standard quitline cessation counseling consisting of 4 proactive counseling calls (but no Cognitive Medication Adherence Counseling (CMAC). | 121 |
| 6 Weeks of Nicotine Patch+Nicotine Gum and CMAC Participants in this randomization group received 6 weeks of nicotine patch plus nicotine gum and standard quitline cessation counseling consisting of 4 proactive counseling calls plus Cognitive Medication Adherence Counseling (CMAC). | 127 |
| Total | 987 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 24 | 28 | 18 | 31 | 27 | 25 | 20 | 24 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 4 | 5 | 4 | 3 | 3 | 5 |
Baseline characteristics
| Characteristic | 2 Weeks of Nicotine Patch Only Plus CMAC | 2 Weeks of Nicotine Patch+Nicotine Gum , No CMAC | 2 Weeks of Nicotine Patch+Nicotine Gum and CMAC | 6 Weeks of Nicotine Patch Only, No CMAC | 2 Weeks of Nicotine Patch Only, No CMAC | 6 Weeks of Nicotine Patch Only Plus CMAC | 6 Weeks of Nicotine Patch+Nicotine Gum , No CMAC | 6 Weeks of Nicotine Patch+Nicotine Gum and CMAC | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Age, Categorical >=65 years | 7 Participants | 2 Participants | 2 Participants | 6 Participants | 4 Participants | 8 Participants | 6 Participants | 4 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 119 Participants | 121 Participants | 119 Participants | 116 Participants | 115 Participants | 119 Participants | 114 Participants | 123 Participants | 946 Participants |
| Age, Continuous | 43.35 years STANDARD_DEVIATION 12.61 | 41.39 years STANDARD_DEVIATION 11.24 | 40.84 years STANDARD_DEVIATION 11.96 | 41.74 years STANDARD_DEVIATION 14.19 | 42.33 years STANDARD_DEVIATION 12.99 | 43.18 years STANDARD_DEVIATION 13.627 | 42.61 years STANDARD_DEVIATION 13.51 | 40.03 years STANDARD_DEVIATION 13.31 | 41.93 years STANDARD_DEVIATION 12.96 |
| Gender Female | 65 Participants | 63 Participants | 70 Participants | 75 Participants | 71 Participants | 72 Participants | 74 Participants | 79 Participants | 569 Participants |
| Gender Male | 61 Participants | 60 Participants | 52 Participants | 47 Participants | 48 Participants | 55 Participants | 47 Participants | 48 Participants | 418 Participants |
| Region of Enrollment United States | 126 participants | 123 participants | 122 participants | 122 participants | 119 participants | 127 participants | 121 participants | 127 participants | 987 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 245 | 0 / 245 | 0 / 249 | 0 / 248 |
| serious Total, serious adverse events | 0 / 245 | 0 / 245 | 0 / 249 | 0 / 248 |
Outcome results
Primary
7-Day Point Prevalence Abstinence From Smoking by Intervention
Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day.
Time frame: 26 weeks after the target quit smoking date
Population: The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention (e.g., 6 wks NRT); this effect size was based on prior quitline studies; we predicted that abstinence rates at 6 months would be approximately 12% in a standard intervention vs. 18.4% in an enhanced intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Two Weeks of Nicotine Replacement Therapy (NRT) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 43.3 Percentage of participants not smoking |
| Six Weeks of Nicotine Replacement Therapy (NRT) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 48.9 Percentage of participants not smoking |
| NRT Monotherapy (Nicotine Patch Only) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 42.3 Percentage of participants not smoking |
| NRT Combination Therapy (Nicotine Patch Plus Nicotine Gum) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 49.9 Percentage of participants not smoking |
| Standard Cessation Counseling (No CMAC) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 47.6 Percentage of participants not smoking |
| Standard Cessation Counseling Plus CMAC) | 7-Day Point Prevalence Abstinence From Smoking by Intervention | 44.6 Percentage of participants not smoking |
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving Two Weeks of Nicotine Replacement Therapy (NRT) versus Six Weeks of Nicotine Replacement Therapy (NRT). We hypothesized that Six Weeks of NRT would result in statistically significantly higher abstinence rates compared to Two Weeks of NRT.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention (e.g., 6 wks NRT).p-value: 0.07695% CI: [0.98, 1.61]Regression, Logistic
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving NRT Monotherapy (Nicotine Patch Only) versus NRT Combination Therapy (Nicotine Patch plus Nicotine Gum). We hypothesized that Combination NRT would result in statistically significantly higher abstinence rates compared to NRT Monotherapy.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention (e.g., Combination NRT).p-value: 0.01795% CI: [1.06, 1.75]Regression, Logistic
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving Standard Cessation Counseling (No CMAC) versus Standard Cessation Counseling plus CMAC. We hypothesized that Standard Counseling plus CMAC would result in statistically significantly higher abstinence rates compared to Standard Counseling Only.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention (e.g., Standard Counseling plus CMAC).p-value: 0.34395% CI: [0.69, 1.14]Regression, Logistic
Primary
7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group
Self-reported total abstinence from any tobacco use (even a single puff) for the seven days preceding the target follow-up day.
Time frame: 26 weeks after the target quit smoking date
Population: The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention (e.g., 6 wks NRT); this effect size was based on prior quitline studies; we predicted that abstinence rates at 6 months would be approximately 12% in a standard intervention vs. 18.4% in an enhanced intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Two Weeks of Nicotine Replacement Therapy (NRT) | 7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group | 38.4 Percentage of participants not smoking |
| Six Weeks of Nicotine Replacement Therapy (NRT) | 7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group | 48.2 Percentage of participants not smoking |
| NRT Monotherapy (Nicotine Patch Only) | 7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group | 46.2 Percentage of participants not smoking |
| NRT Combination Therapy (Nicotine Patch Plus Nicotine Gum) | 7-Day Point Prevalence Abstinence From Smoking by Nicotine Replacement Therapy (NRT) Group | 51.6 Percentage of participants not smoking |
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving Two Weeks of Nicotine Replacement Therapy (NRT) Monotherapy (Nicotine Patch Only) versus Two Weeks of Combination NRT (Patch+Gum). We hypothesized that Two Weeks of Combination NRT would result in statistically significantly higher abstinence rates compared to Two Weeks of NRT Monotherapy.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention.p-value: 0.02995% CI: [1.04, 2.14]Regression, Logistic
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving Two Weeks of Nicotine Replacement Therapy (NRT) Monotherapy (Nicotine Patch Only) versus SIx Weeks of NRT Monotherapy. We hypothesized that Six Weeks of NRT Monotherapy would result in statistically significantly higher abstinence rates compared to Two Weeks of NRT Monotherapy.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention.p-value: 0.07995% CI: [0.96, 1.97]Regression, Logistic
Comparison: Null hypothesis: No difference in abstinence rates for participants receiving Two Weeks of Nicotine Replacement Therapy (NRT) Monotherapy (Nicotine Patch Only) versus Six Weeks of Combination NRT (Patch+Gum). We hypothesized that Six Weeks of Combination NRT would result in statistically significantly higher abstinence rates compared to Two Weeks of NRT Monotherapy.~The study was originally powered to detect at least a 6.4% increase in the abstinence rate due to an enhanced intervention.p-value: 0.00395% CI: [1.2, 2.45]Regression, Logistic
Secondary
Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group
For cost analyses, we computed the costs of intervention per caller, the cost per quit based on the 6-month ITT 7-day PPA, and the incremental cost-effectiveness ratio (ICER. Intervention costs included direct costs associated with registration, provision of NRT and counseling (standard and MAC), and mailing of a quit guide (all participants) and a MAC information sheet (MAC participants only). Facility space, supplies, and physician supervision time were included in the call costs; research-related costs were excluded. ICER ratio is a measure of the added cost per added quit for two treatments. ICER was computed as the cost difference between the least intensive treatment group (2 weeks of nicotine patch only) and a more intensive comparison group divided by the difference in the quit rates of the two groups being compared; e.g., the ICER for the group that received 2 weeks of nicotine patch and nicotine gum = (213-178)/(.482-.384) = $357.
Time frame: 26 weeks after the target quit smoking date
Population: No a priori power analysis was conducted for this secondary outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Two Weeks of Nicotine Replacement Therapy (NRT) | Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group | 94 U.S. Dollars |
| Six Weeks of Nicotine Replacement Therapy (NRT) | Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group | 118 U.S. Dollars |
| NRT Monotherapy (Nicotine Patch Only) | Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group | 115 U.S. Dollars |
| NRT Combination Therapy (Nicotine Patch Plus Nicotine Gum) | Incremental Cost-Effectiveness Ratio for 7-Day Point Prevalence Abstinence From Smoking at 26 Weeks Post-Quit by Nicotine Replacement Therapy (NRT) Group | 128 U.S. Dollars |
Comparison: In this analysis, the Incremental cost-effectiveness ratio (ICER) is computed. ICER is a measure of the added cost per added quit for two treatments. ICER was computed as the cost difference between the least intensive treatment group (2 weeks of nicotine patch only) and a more intensive comparison group divided by the difference in the quit rates of the two groups being compared; ICER for the group that received 6 weeks of nicotine patch and nicotine gum = (348-178)/(.516-.384) = $1290.Incremental cost-effectiveness ratio
Comparison: In this analysis, the incremental cost-effectiveness ratio (ICER) is computed. ICER is a measure of the added cost per added quit for two treatments. ICER was computed as the cost difference between the least intensive treatment group (2 weeks of nicotine patch only) and a more intensive comparison group divided by the difference in the quit rates of the two groups being compared; ICER for the group that received 2 weeks of nicotine patch and nicotine gum = (213-178)/(.482-.384) = $357.Incremental cost-effectiveness ratio
Comparison: In this analysis, the incremental cost-effectiveness ratio (ICER) is computed. ICER is a measure of the added cost per added quit for two treatments. ICER was computed as the cost difference between the least intensive treatment group (2 weeks of nicotine patch only) and a more intensive comparison group divided by the difference in the quit rates of the two groups being compared; ICER for the group that received 6 weeks of nicotine patch only = (233-178)/(.462-.384) = $712.Incremental cost-effectiveness ratio