Christine L. Baker

Cost-Utility Analysis of Varenicline versus Existing Smoking Cessation Strategies using the BENESCO Simulation Model: Application to a Population of US Adult Smokers

BackgroundOf 1 346 700 total deaths each year in the US, an estimated 440 100 are smoking related, making it the leading preventable cause of premature death in the US. Despite the health and economic benefits of smoking cessation being well documented, reimbursement coverage for smoking cessation therapies is generally limited in the US and elsewhere.ObjectivesTo evaluate the cost effectiveness of varenicline, an α4ß2 nicotinic acetylcholine receptor partial agonist, recently approved to aid smoking cessation.MethodsA Markov model, the Benefits of Smoking Cessation on Outcomes (BENESCO) model, was developed to simulate the lifetime direct costs and consequences of a hypothetical cohort of US adult smokers who make a one-time attempt to quit smoking. The smoking cessation strategies compared were varenicline, bupropion, nicotine replacement therapy and unaided quitting. The model used the hazard ratios from the Cancer Prevention Study (CPS)-II study for the mortality of smoking-related diseases as a proxy to calculate the relative risks of the incidence and prevalence of these diseases, following previously developed methodology. The costs (year 2005 values) and utilities for the included smoking-related diseases (lung cancer, chronic obstructive lung disease [COPD], coronary heart disease [CHD], stroke and asthma exacerbations), and the efficacies of the smoking cessation strategies, were sourced from the published literature. Costs and benefits were discounted at 3% pa. Probabilistic and univariate sensitivity analyses were conducted.ResultsVarenicline was found to dominate all other smoking cessation strategies that were investigated for both the 20-year and lifetime timeframe. Furthermore, if 25% of the current population of US smokers made a one-time attempt to quit using varenicline compared with unaided cessation, almost 144 000 smoking-related deaths and over 261 000 cases of asthma exacerbations, COPD, CHD, stroke and lung cancer could be avoided compared with an unaided smoking cessation strategy.ConclusionsVarenicline, a recently approved therapy for smoking cessation, is likely to be a cost-effective alternative compared with currently available options.

Revealing the multidimensional framework of the Minnesota nicotine withdrawal scale.

ABSTRACT Objectives: The version of the Minnesota Nicotine Withdrawal Scale (MNWS) under consideration consists of nine items. No psychometric analyses of this version have been published. The objectives of this investigation were to perform a factor analysis and to further assess the psychometric properties of the MNWS. Research design and methods: Data came from three Phase II clinical trials on varenicline, developed for smoking cessation, in a sample of smokers. Exploratory factor analysis was used to examine the structure of the MNWS in the first completed study ( n = 626) over various time periods. The postulated factor structure was then tested in a set of confirmatory analyses conducted on two subsequent studies ( n = 627, n = 312). The proposed structure was further evaluated through construct validity and reliability analyses. Main outcome measures: The nine items of the MNWS included the following: urge to smoke (craving); depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; and difficulty staying asleep. Each item was rated by a subject on an ordinal scale from 0 (not at all) to 4 (extreme). Results: Scree plots and rotated factor patterns from the exploratory factor analyses revealed two multi-item domains – Negative Affect with four items and Insomnia with two items – and three individual items (Craving, Restlessness, Increased Appetite). Confirmatory factor analyses supported the structure with fit indexes exceeding 0.90. The multidimensional framework of the MNWS correlated as expected with health status, depicted an expected course of withdrawal symptoms over time, predicted the sensitivity of withdrawal symptoms on subsequent cessation, and produced internal reliability estimates above 0.70. Conclusions: Evidence is obtained to support the validity and reliability of the multidimensional structure of the nine-item MNWS. The data suggest that the MNWS has individual constructs on Negative Affect (depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating), Insomnia (difficulty going to sleep; difficulty staying asleep), Craving, Restlessness, and Increased Appetite. As such, analyzing each construct separately would strengthen the analysis of the popular MNWS.

Recent trends in exposure to secondhand smoke in the United States population

BackgroundPrevious research using the National Health and Nutrition Examination Surveys (NHANES) data documented a significant downward trend in secondhand smoke (SHS) exposure between 1988 and 2002. The objective of this study was to assess whether the downward trend in exposure continued from 2001 through 2006.MethodsWe analyzed data from the 2001-2006 NHANES to estimate exposure of nonsmokers to SHS. Geometric means of serum cotinine levels for all nonsmokers were computed.ResultsOverall serum cotinine levels (95% Confidence Intervals) in 2001-2002, 2003-2004, and 2005-2006 were 0.06 ng/mL (0.05-0.07), 0.07 ng/mL (0.06-0.09), and 0.05 ng/mL (0.05-0.06), respectively. Subgroup analysis by age, gender, and race/ethnicity groups showed similar trends in cotinine levels. Children, males, and non-Hispanic Blacks had higher cotinine levels than adults, females, and non-Hispanic Whites and Mexican Americans, respectively. Insignificant P values from the Wald test indicate that serum cotinine levels did not differ over time.ConclusionsThe long-term trend of declining exposure to SHS among nonsmokers appears to have leveled off. However, disparities noted in previous research persist today, with the young, non-Hispanic Blacks, and males experiencing higher levels of exposure.

Changes in health-related quality of life with smoking cessation treatment

BACKGROUND Cigarette smoking causes reduced health-related quality of life (QoL) and smoking abstinence improves health-related QoL. We assessed the effects of treatment for tobacco dependence on the health-related QoL in a 52-week randomized controlled trial of varenicline and bupropion sustained release (SR). METHODS Subjects who smoked ≥10 cigarettes per day for the past year were randomly assigned to receive varenicline 1 mg twice daily (n = 696), bupropion SR 150 mg twice daily (n = 671) or placebo (n = 685) for 12 weeks and followed post-therapy for an additional 40 weeks. Health-related QoL was assessed using the Smoking Cessation Quality of Life questionnaire at baseline and Weeks 12, 24 and 52. RESULTS Health transition (perceived health compared with baseline) and self-control were both significantly improved among subjects receiving varenicline and bupropion SR compared with placebo at Weeks 12, 24 and 52. Similarly, varenicline-treated subjects had significantly improved health transition and self-control compared with subjects who received bupropion SR at Weeks 12 and 24, and at Week 52 for health transition. A significant positive association existed between length of continuous abstinence and improved health transition, vitality, self-control, anxiety and overall mental profile. In most instances both a direct and an indirect effect (through continuous smoking abstinence) of each active treatment (vs. placebo) contributed to improved self-control and health transition. CONCLUSION Treatment with varenicline and bupropion SR for smoking cessation resulted in improved self-control and health transition that was mediated in large part by continuous smoking abstinence.

Real-world characterization and differentiation of the Global Initiative for Chronic Obstructive Lung Disease strategy classification

Background This study aimed to characterize and differentiate the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy 2011 cut points through the modified Medical Research Council dyspnea scale (mMRC) and chronic obstructive pulmonary disease (COPD) assessment test (CAT). Methods Analysis of COPD patient data from the 2012 Adelphi Respiratory Disease Specific Program was conducted in Europe and US. Matched data from physicians and patients included CAT and mMRC scores. Receiver operating characteristic curves and kappa analysis determined a cut point for CAT and mMRC alignment and thus defined patient movement (“movers”) within GOLD groups A–D, depending on the tool used. Logistic regression analysis, with a number of physician- and patient-reported covariates, characterized those movers. Results Comparing GOLD-defined high-symptom patients using mMRC and CAT cut points (≥2 and ≥10, respectively), there were 890 (53.65%) movers; 887 of them (99.66%) moved from less symptomatic GOLD groups A and C (using mMRC) to more symptomatic groups B and D (using CAT). For receiver operating characteristic (area under the curve: 0.82, P<0.001) and kappa (maximized: 0.45) recommended CAT cut points of ≥24 and ≥26, movers reduced to 429 and 403 patients, respectively. Logistic regression analysis showed variables significantly associated with movers were related to impact on normal life, age, cough, and sleep (all P<0.05). Within movers, direction of movement was significantly associated with the same variables (all P<0.05). Conclusion Use of current mMRC or CAT cut points leads to inconsistencies for COPD assessment classification. It is recommended that cut points are aligned and both tools administered simultaneously for optimal patient care and to allow for closer management of movers. Our research may suggest an opportunity to investigate a combined score approach to patient management based on the worst result of mMRC and CAT. The reduced number of remaining movers may then identify patients who have greater impact of disease and may require a more personalized treatment plan.

Outcomes associated with initiation of tiotropium or fluticasone/salmeterol in patients with chronic obstructive pulmonary disease

Introduction: Adherence to long-acting bronchodilator therapy for management of chronic obstructive pulmonary disease (COPD) is a critical clinical and cost issue. Low adherence is associated with relatively higher exacerbation rates and illness burden. Purpose: To compare adherence between patients with COPD initiating therapy on tiotropium or fluticasone/salmeterol and examine the association between adherence and respiratory-related costs. Patients and methods: This retrospective claims data analysis evaluated patients initiating tiotropium or combination fluticasone/salmeterol from December 1, 2004 to December 31, 2005. Patients had ≥1 COPD diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 491.xx, 492.x, 496) and were observed during 6-month pre-index and variable (12–18-month) post-index periods. Outcomes were adherence to and discontinuation of therapy, and respiratory-related inpatient, medical, and total health care costs. Adherence was medication possession ratio ≥0.80. Discontinuation, adherence, and costs were analyzed with Cox proportional hazards regression, logistic regression, and generalized linear model regressions, respectively. Regressions controlled for demographic, sociodemographic, and health status factors. Results: The study population comprised 1561 tiotropium and 2976 fluticasone/salmeterol patients. In unadjusted comparisons: 19.5% and 8.5% of tiotropium and fluticasone/salmeterol patients, respectively, were adherent (P < 0.001); tiotropium patients versus fluticasone/salmeterol patients had higher mean respiratory-related pharmacy costs (US

Cost effectiveness of tiotropium for chronic obstructive pulmonary disease: a systematic review of the evidence

1080 versus US

Budgetary Impact of Varenicline in Smoking Cessation in the United Kingdom

974, P = 0.002) and health care costs (US

Adjusting for COPD severity in database research: developing and validating an algorithm

3751 versus US

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

2932, P = 0.031). Regression analysis showed tiotropium patients were 31.6% less likely to discontinue therapy (95% confidence interval [CI]: 0.64–0.73) and had 2.25 times higher odds of adherence (CI: 1.85–2.73) versus fluticasone/salmeterol patients. The associations between index therapy and costs were not significant. Adherence versus nonadherence was associated with: 46.9% higher health care costs (CI: 1.13–1.91); 37.1% lower medical costs (CI: 0.43–0.91); and 53.4% lower inpatient costs (CI: 0.30–0.72). Conclusion: Patients with COPD initiating long-acting bronchodilator therapy were more likely to be adherent to tiotropium than to fluticasone/salmeterol. Adherence to either tiotropium or to fluticasone/salmeterol was associated with lower respiratory-related medical and inpatient costs, and with higher respiratory-related total health care costs.