A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan.

INTRODUCTION: The objective of the study was to evaluate the cost-effectiveness of glecaprevir/pibrentasvir versus other direct-acting antivirals (DAAs) for treating chronic hepatitis C virus (HCV) infections in Japan. METHODS: We developed a health state transition model to capture the natural history of HCV. A cost-effectiveness analysis of DAAs from the perspective of a public healthcare payer in Japan with a lifetime horizon over annual cycles was performed. Treatment attributes, baseline demographics, transition probabilities, health-state utilities, and costs data were extracted from publications. Costs and outcomes were discounted at 2% per annum. In the base case we focused on genotype 1 (GT1) treatment-naïve patients without cirrhosis. The scenario analysis examined a pan-genotype treatment in GT1-3 (i.e., portfolio), treatment-naïve, and treatment-experienced patients. The portfolio cost-effectiveness of DAAs was derived by calculating a weighted average of patient segments defined by treatment history, cirrhosis status, and genotype. RESULTS: The base case results indicated that glecaprevir/pibrentasvir was dominant (i.e., generating higher quality-adjusted life years [QALYs] and lower lifetime costs) compared to all other DAAs. The predicted lifetime risk of hepatocellular carcinoma was 3.66% for glecaprevir/pibrentasvir and sofosbuvir/ledipasvir, 4.99% for elbasvir/grazoprevir, and 5.27% for daclatasvir/asunaprevir/beclabuvir. In scenario analysis the glecaprevir/pibrentasvir (GLE/PIB) portfolio dominated the sofosbuvir (SOF)-based portfolio (namely sofosbuvir/ledipasvir in GT1-2 and sofosbuvir + ribavirin in GT3). The base case probabilistic sensitivity analysis (PSA) showed that glecaprevir/pibrentasvir was cost-effective in 93.4% of the simulations for a willingness-to-pay/QALY range of Japanese yen (JPY) 1.6-20 million. The PSA for the portfolio scenario indicated that the GLE/PIB portfolio was cost-effective in 100% of simulations until the willingness-to-pay/QALY reached JPY 5.2 million; this proportion decreased to 69.4% at a willingness-to-pay/QALY of JPY 20 million. Results were also robust in deterministic sensitivity analyses. CONCLUSION: In GT1 treatment-naïve non-cirrhotic patients GLE/PIB was a cost-effective strategy compared to other DAAs. When a pan-genotypic framework was used, the GLE/PIB portfolio dominated the SOF-based portfolio.

Cost-Effectiveness of Elbasvir/Grazoprevir Versus Daclatasvir Plus Asunaprevir in Patients with Chronic Hepatitis C Virus Genotype 1b Infection in China.

BACKGROUND AND OBJECTIVE: New direct-acting antivirals (DAAs) have high efficacy and tolerability in the treatment of hepatitis C virus (HCV) infection. The objective of this study was to assess the cost-effectiveness of elbasvir/grazoprevir (EBR/GZR) versus daclatasvir plus asunaprevir (DCV + ASV) in Chinese patients with chronic HCV genotype (GT) 1b infection stratified by cirrhosis status and treatment history. METHODS: A cohort state-transition model was constructed to simulate the course of chronic HCV infection in patients stratified by cirrhosis status and treatment history. The model projected lifetime outcomes and costs in terms of HCV treatment, laboratory tests, clinical procedures, and hospitalizations. Mean age of the study cohort at baseline was 45 years, based on published sources. Sustained virologic response (SVR) rates were derived from clinical trials. Healthcare resource utilization and health utilities were extracted or estimated from published studies in Chinese populations. The stability of the base-case analysis was validated by deterministic and probabilistic sensitivity analyses. RESULTS: In each subpopulation of Chinese patients, treatment with EBR/GZR dominated treatment with DCV + ASV, with lower costs and higher quality-adjusted life-years (QALYs). Sensitivity analysis demonstrated that EBR/GZR was the cost-effective option compared to DCV + ASV in 77.4-97.4% or 94.1-100% of model simulations in Chinese treatment-naïve or treatment-experienced patients, respectively, as the cost-effectiveness threshold changed from zero to US$24,150/QALY (three times GDP per capita in China). CONCLUSIONS: Treatment with EBR/GZR was the cost-effective option for patients with chronic HCV GT1b infection in China, regardless of cirrhosis status or treatment history.

Glecaprevir/pibrentasvir expands reach while reducing cost and duration of hepatitis C virus therapy.

Hepatitis C virus (HCV) treatments have dramatically progressed from poorly tolerated, moderately successful interferon-based therapies to highly effective all-oral interferon-free regimens. While sustained virologic responses have significantly improved with fixed-dose combinations (FDC) of these direct-acting antivirals (DAA), cost remains high and certain populations of patients remain difficult to treat. Glecaprevir (GLE, an NS3/4A protease inhibitor) and pibrentasvir (PIB, NS5A inhibitor) were recently approved as a FDC therapy for HCV, and have expanded reach, reduced cost, and in certain populations, reduced HCV treatment duration. GLE/PIB is effective across all genotypes, and has been shown to be effective in HIV-infected patients, patients with chronic kidney disease, and Child-Pugh A-compensated cirrhosis. GLE/PIB is also effective for a shortened duration of 8 weeks in treatment-naive non-cirrhotic patients.

Economic evaluation of Zepatier for the management of HCV in the Italian scenario.

BACKGROUND: Hepatitis C virus (HCV) is a major health issue worldwide. New generation of direct-active antiviral medications is an epoch-making turning point in the management of HCV infections. OBJECTIVE: Conducing a cost-effectiveness analysis comparing the combination of elbasvir/grazoprevir and sofosbuvir + pegylated interferon/ribavirin for the management of all HCV patients (even those in the initial stages of fibrosis). METHODS: A Markov model was built on the natural history of the disease to assess the efficacy of the alternatives. The outcomes are expressed in terms of quality adjusted life-years (QALYs) and result in terms of incremental cost-effectiveness ratio). RESULTS: Elbasvir/grazoprevir implies an expenditure of €21,104,253.74 with a gain of 19,287.90 QALYs and sofosbuvir + pegylated interferon/ribavirin implies an expenditure of €31,904,410.11 with a gain of 18,855.96 QALYs. Elbasvir/grazoprevir is thus a dominant strategy. CONCLUSION: Consideration should be given to the opportunity cost of not treating patients with a lower degree of fibrosis (F0-F2).

Cost-effectiveness analysis of elbasvir-grazoprevir regimen for treating hepatitis C virus genotype 1 infection in stage 4-5 chronic kidney disease patients in France.

OBJECTIVE: To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. DESIGN: This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained. PATIENTS: The mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis. INTERVENTION: Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment. RESULTS: EBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis. CONCLUSIONS: This cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naïve or experienced patients with chronic hepatitis C genotype 1 and stage 4-5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment.

Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection.

OBJECTIVE: To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. METHODS: A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. CONCLUSIONS: Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations.

Cost-effectiveness of elbasvir/grazoprevir use in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and chronic kidney disease in the United States.

Among patients with chronic kidney disease (CKD) in the United States, HCV infection causes significant morbidity and mortality and results in substantial healthcare costs. A once-daily oral regimen of elbasvir/grazoprevir (EBR/GZR) for 12 weeks was found to be a safe and efficacious treatment for HCV in patients with CKD. We evaluated the cost-effectiveness of EBR/GZR in treatment-naïve and treatment-experienced CKD patients compared with no treatment (NoTx) and pegylated interferon plus ribavirin (peg-IFN/RBV) using a computer-based model of the natural history of chronic HCV genotype 1 infection, CKD and liver disease. Data on baseline characteristics of the simulated patients were obtained from NHANES, 2000-2010. Model inputs were estimated from published studies. Cost of treatment with EBR/GZR and peg-INF/RBV were based on wholesale acquisition cost. All costs were from a third-party payer perspective and were expressed in 2015 U.S. dollars. We estimated lifetime incidence of liver-related complications, liver transplantation, kidney transplantation, end-stage live disease mortality and end-stage renal disease mortality; lifetime quality-adjusted life years (QALY); and incremental cost-utility ratios (ICUR). The model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV genotype 1 infection and CKD compared with NoTx or use of peg-IFN/RBV. EBR/GZR-based regimens resulted in higher average remaining QALYs and higher costs (11.5716, $191 242) compared with NoTx (8.9199, $156 236) or peg-INF/RBV (10.2857, $186 701). Peg-IFN/RBV is not cost-effective, and the ICUR of EBR/GZR compared with NoTx was $13 200/QALY. Treatment of a patient on haemodialysis with EBR/GZR resulted in a higher ICUR ($217 000/QALY). Assuming a threshold of $100 000 per QALY gained for cost-effectiveness, use of elbasvir/grazoprevir to treat an average patient with CKD can be considered cost-effective in the United States.

Funding a smoking cessation program for Crohn's disease: an economic evaluation.

OBJECTIVES: Patients with Crohn's disease (CD) who smoke are at a higher risk of flaring and requiring surgery. Cost-effectiveness studies of funding smoking cessation programs are lacking. Thus, we performed a cost-utility analysis of funding smoking cessation programs for CD. METHODS: A cost-utility analysis was performed comparing five smoking cessation strategies: No Program, Counseling, Nicotine Replacement Therapy (NRT), NRT+Counseling, and Varenicline. The time horizon for the Markov model was 5 years. The health states included medical remission (azathioprine or antitumor necrosis factor (anti-TNF), dose escalation of an anti-TNF, second anti-TNF, surgery, and death. Probabilities were taken from peer-reviewed literature, and costs (CAN$) for surgery, medications, and smoking cessation programs were estimated locally. The primary outcome was the cost per quality-adjusted life year (QALY) gained associated with each smoking cessation strategy. Threshold, three-way sensitivity, probabilistic sensitivity analysis (PSA), and budget impact analysis (BIA) were carried out. RESULTS: All strategies dominated No Program. Strategies from most to least cost effective were as follows: Varenicline (cost: $55,614, QALY: 3.70), NRT+Counseling (cost: $58,878, QALY: 3.69), NRT (cost: $59,540, QALY: 3.69), Counseling (cost: $61,029, QALY: 3.68), and No Program (cost: $63,601, QALY: 3.67). Three-way sensitivity analysis demonstrated that No Program was only more cost effective when every strategy's cost exceeded approximately 10 times their estimated costs. The PSA showed that No Program was the most cost-effective <1% of the time. The BIA showed that any strategy saved the health-care system money over No Program. CONCLUSIONS: Health-care systems should consider funding smoking cessation programs for CD, as they improve health outcomes and reduce costs.

Brimonidine for erythema caused by rosacea.

Brimonidine gel (Mirvaso-Galderma) became available in February of this year for the symptomatic treatment of facial erythema associated with rosacea in adults.1 Here, we review the evidence on brimonidine gel and consider its place in the management of erythema associated with rosacea.

A pragmatic, randomized, controlled study evaluating the impact of access to smoking cessation pharmacotherapy coverage on the proportion of successful quitters in a Canadian population of smokers motivated to quit (ACCESSATION).

BACKGROUND: Many smokers find the cost of smoking cessation medications a barrier. Financial coverage for these medications increases utilization of pharmacotherapies. This study assesses whether financial coverage increases the proportion of successful quitters. METHODS: A pragmatic, open-label, randomized, controlled trial was conducted in 58 Canadian sites between March 2009 and September 2010. Smokers (≥10 cigarettes/day) without insurance coverage who were motivated to quit within 14 days were randomized (1:1) in a blinded manner to receive either full coverage eligibility for 26 weeks or no coverage. Pharmacotherapies covered were varenicline, bupropion, or nicotine patches/gum. Investigators/subjects were unblinded to study group assignment after randomization and prior to choosing a smoking cessation method(s). All subjects received brief smoking cessation counseling. The primary outcome measure was self-reported 7-day point prevalence of abstinence (PPA) at week 26. RESULTS: Of the 1380 randomized subjects (coverage, 696; no coverage, 684), 682 (98.0%) and 435 (63.6%), respectively, were dispensed at least one smoking cessation medication dose. The 7-day PPA at week 26 was higher in the full coverage versus no coverage group: 20.8% (n = 145) and 13.9% (n = 95), respectively; odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.23-2.18; p = 0.001. Urine cotinine-confirmed 7-day PPA at week 26 was 15.7% (n = 109) and 10.1% (n = 69), respectively; OR = 1.68, 95% CI 1.21-2.33; p = 0.002. After pharmacotherapy, coverage eligibility was withdrawn from the full coverage group, continuous abstinence between weeks 26 and 52 was 6.6% (n = 46) and 5.6% (n = 38), in the full coverage and no coverage groups, respectively; OR = 1.19, 95% CI 0.76-1.87; p = 0.439. CONCLUSIONS: In this study, the adoption of a smoking cessation medication coverage drug policy was an effective intervention to improve 26-week quit rates in Canada. The advantages were lost once coverage was discontinued. Further study is required on the duration of coverage to prevent relapse to smoking. (clinicaltrials.gov identifier: NCT00818207; the study was sponsored by Pfizer Inc.).

Association of out-of-pocket pharmacy costs with adherence to varenicline.

BACKGROUND: Varenicline, a nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To date, no research has examined the relationship between out-of-pocket (OOP) expense and varenicline adherence among Medicare beneficiaries. OBJECTIVES: To (a) characterize medication utilization patterns of varenicline among Medicare members newly initiated on varenicline and (b) examine the relationship between member OOP expense and varenicline medication adherence. METHODS: In this retrospective cohort study, pharmacy claims data were used to identify Medicare Advantage Prescription Drug Plan (MAPD) members newly initiated on varenicline. Demographic and clinical characteristics, varenicline medication utilization patterns, and pharmacy costs (total and varenicline-specific) were determined for members included in the study. Varenicline adherence was measured by calculating the proportion of days covered (PDC) over a period of 84 days (12 weeks) after initiation. Multiple regression analysis was used to examine the relationship between varenicline OOP cost and varenicline medication utilization, while controlling for sociodemographic characteristics, clinical factors, and nonvarenicline pharmacy costs. RESULTS: A total of 15,452 MAPD members were included in the analysis. Mean (SD) subject age was 62.6 (10.0) years; 21.1% (n = 3,256) were dual eligible; and 33.0% (n = 5,106) received a low-income subsidy. Mean (SD) initial varenicline treatment episode duration was 50.8 (37.8) days, with a mean (SD) varenicline days' supply of 47.8 (32.6) obtained by members during the initial treatment episode. Mean (SD) PDC was 0.51 (0.24), and 14.9% (n = 2,302) of members were classified as adherent to treatment (PDC ≥ 0.80). Greater varenicline OOP expense was significantly associated with lower PDC (regression coefficient = -0.058, P less than 0.001) and significantly associated with lower odds of receiving a refill for varenicline (odds ratio 0.594, 95% CI: 0.540-0.655, P less than 0.001). CONCLUSIONS: Among Medicare beneficiaries newly initiated on varenicline, medication adherence was suboptimal, and greater OOP cost was associated with lower adherence and lower odds of refilling varenicline.

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation.

BACKGROUND: Tobacco smoking is one of the leading causes of deaths worldwide. Nearly one-fifth of adults in the UK regularly smoke cigarettes. The ill-health associated with smoking costs the NHS over £3B every year. A number of pharmacological interventions are available that can help people to quit smoking. These include nicotinic receptor partial agonists such as varenicline or cytisine. Varenicline is a synthetic product licensed for use in the UK, while cytisine is derived naturally from the seeds of the plant Cytisus laborinum L. (golden rain acacia). OBJECTIVES: To review the evidence on the clinical effectiveness and safety of cytisine from smoking cessation compared with varenicline; to develop an economic model to estimate the cost-effectiveness of cytisine and varenicline; and to provide recommendations based on value of information analyses as to whether or not a head-to-head trial of cytisine and varenicline would represent effective use of resources. DATA SOURCES: Efficacy and adverse events data were sourced from a recent Cochrane review. These data were supplemented with an updated search of twelve electronic databases, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and The Cochrane Library, for the period from December 2011 to January 2013. The review included randomised controlled trials (RCTs) of adult smokers attempting to quit using varenicline or cytisine. Further interventions were considered (placebo, nicotine replacement therapy, bupropion) to allow an indirect comparison between varenicline and cytisine. The primary outcome was abstinence at a minimum of 6 months' follow-up. Secondary outcomes were common adverse events such as abnormal dreams, headache, nausea, insomnia and serious adverse events. REVIEW METHODS: A systematic review and network meta-analysis of the clinical evidence was undertaken. A random-effects model was used to allow for heterogeneity between studies. The economic model structure was based on a published model. Probabilistic sensitivity analyses were undertaken to estimate the treatment expected to be most cost-effective given current information. Formal expected value of perfect information, perfect partial information and of sample information were performed. RESULTS: Twenty-three (RCTs) were included in the systematic review, comprising a total of 10,610 participants. Twenty-one trials of varenicline of differing dosing schedules and two trials of cytisine at standard dose met the inclusion criteria. No head-to-head trials comparing varenicline with cytisine were identified. The methodological quality of the studies was judged to be moderate to good. Cytisine was more efficacious than placebo [hazard ratio (HR) 4.27, 95% credible interval (CrI) 2.05 to 10.05], as was standard-dose varenicline (HR 2.58, 95% Crl 2.16 to 3.15). Standard-dose varenicline treatment was associated with significantly higher rates of headache, insomnia and nausea than placebo; there was no significant difference in the rates of abnormal dreams. There were no significant differences in the rates of headache or nausea between cytisine and placebo; data were identified for neither abnormal dreams nor insomnia. Using expected values, cytisine is anticipated to dominate varenicline, in that it produces more quality-adjusted life-years at a lower associated cost. This occurred in approximately 90% of the scenarios performed. However, owing to the large number of people who wish to quit smoking (estimated to be 3 million over a 10-year period), the implications of making an incorrect decision is large. The expected value of sample information indicated that conducting a head-to-head trial of cytisine and varenicline was worthwhile, and that 1000 smokers per arm was an appropriate number to recruit. CONCLUSIONS: On the basis of the evidence included in this review, varenicline and cytisine are both effective interventions to aid smoking cessation when compared with placebo. Cytisine is estimated to be both more clinically effective and cost-effective than varenicline. However, there is uncertainty in the decision, and a head-to-head trial of cytisine and varenicline would appear to be an effective use of resources. STUDY REGISTRATION: The study was registered as PROSPERO CRD42012003455. FUNDING DETAILS: The National Institute for Health Research Health Technology Assessment programme.

Impact of access restrictions on varenicline utilization.

AIM: To assess the impact of access restrictions on varenicline utilization. METHODS: Employer-sponsored health plans contributing to the MarketScan Commercial Claims and Encounters Database were categorized according to 2009 varenicline access restrictions: no coverage; prior authorization; smoking cessation program requirement; no restrictions. The cohort comprised all adults continuously enrolled in plans during 2009. Each restriction cohort was compared with the no restrictions cohort using descriptive analyses. Data were assessed using logistic regression; demographic and clinical characteristics were covariates. RESULTS: In this study (no coverage, n = 454,419; prior authorization, n = 171,530; smoking cessation program, n = 108,181; no restrictions, n = 607,389), compared with the no restrictions cohort, the odds of treatment were 71% lower (odds ratio: 0.29; 95% CI: 0.26, 0.31) in the smoking cessation program cohort (p < 0.001) and 80% lower (odds ratio: 0.20; 95% CI: 0.19, 0.22) in the prior authorization cohort (p < 0.001). CONCLUSIONS: Access restrictions were associated with significantly lower odds for varenicline utilization.

Smoking cessation treatment and outcomes patterns simulation: a new framework for evaluating the potential health and economic impact of smoking cessation interventions.

BACKGROUND: Most existing models of smoking cessation treatments have considered a single quit attempt when modelling long-term outcomes. OBJECTIVE: To develop a model to simulate smokers over their lifetimes accounting for multiple quit attempts and relapses which will allow for prediction of the long-term health and economic impact of smoking cessation strategies. METHODS: A discrete event simulation (DES) that models individuals' life course of smoking behaviours, attempts to quit, and the cumulative impact on health and economic outcomes was developed. Each individual is assigned one of the available strategies used to support each quit attempt; the outcome of each attempt, time to relapses if abstinence is achieved, and time between quit attempts is tracked. Based on each individual's smoking or abstinence patterns, the risk of developing diseases associated with smoking (chronic obstructive pulmonary disease, lung cancer, myocardial infarction and stroke) is determined and the corresponding costs, changes to mortality, and quality of life assigned. Direct costs are assessed from the perspective of a comprehensive US healthcare payer ($US, 2012 values). Quit attempt strategies that can be evaluated in the current simulation include unassisted quit attempts, brief counselling, behavioural modification therapy, nicotine replacement therapy, bupropion, and varenicline, with the selection of strategies and time between quit attempts based on equations derived from survey data. Equations predicting the success of quit attempts as well as the short-term probability of relapse were derived from five varenicline clinical trials. RESULTS: Concordance between the five trials and predictions from the simulation on abstinence at 12 months was high, indicating that the equations predicting success and relapse in the first year following a quit attempt were reliable. Predictions allowing for only a single quit attempt versus unrestricted attempts demonstrate important differences, with the single quit attempt simulation predicting 19 % more smoking-related diseases and 10 % higher costs associated with smoking-related diseases. Differences are most prominent in predictions of the time that individuals abstain from smoking: 13.2 years on average over a lifetime allowing for multiple quit attempts, versus only 1.2 years with single quit attempts. Differences in abstinence time estimates become substantial only 5 years into the simulation. In the multiple quit attempt simulations, younger individuals survived longer, yet had lower lifetime smoking-related disease and total costs, while the opposite was true for those with high levels of nicotine dependence. CONCLUSION: By allowing for multiple quit attempts over the course of individuals' lives, the simulation can provide more reliable estimates on the health and economic impact of interventions designed to increase abstinence from smoking. Furthermore, the individual nature of the simulation allows for evaluation of outcomes in populations with different baseline profiles. DES provides a framework for comprehensive and appropriate predictions when applied to smoking cessation over smoker lifetimes.

Cost-effectiveness of varenicline versus bupropion, nicotine-replacement therapy, and unaided cessation in Greece.

BACKGROUND: Varenicline was designed to relieve symptoms of nicotine withdrawal, including cigarette craving, and to block the reinforcing effects of continued nicotine use. The cost-effectiveness of varenicline in some countries has not been studied. OBJECTIVE: The aim of this study was to compare the cost-effectiveness of varenicline to that of bupropion, nicotine-replacement therapy (NRT), and unaided cessation in the Greek health care setting. The analysis takes into account a societal security (third-party payer) perspective. METHODS: To perform the analyses of the benefits of smoking cessation in terms of smoking-related morbidity, mortality, and associated medical costs, a Markov model was used that simulated the progress of a hypothetical cohort of current smokers making a single attempt to quit smoking at the beginning of the timeframe of the analysis. The robustness of the results was assessed using a series of 1-way sensitivity analyses. RESULTS: Varenicline was associated with the potential prevention of 14.1, 14.2, and 35.1 additional cases of the 4 smoking-related diseases incorporated into the model, per 1000 smokers willing to quit, versus bupropion, NRT, and unaided cessation, respectively. Potentially avoided smoking-related deaths with varenicline were estimated at 3.24, 3.26, and 7.5 per 1000 quitters versus the 3 comparators. Varenicline led to a potential gain of 33.78, 33.91, and 83.97 QALYs per 1000 persons willing to make a quit attempt versus the 3 comparators. Varenicline was associated with cost-savings against both active comparators for the lifetime horizon. Overall, the cost per additional quitter with varenicline, considering only the costs of the smoking-cessation strategy, was €2659 (€1015) for a lifetime horizon compared with bupropion (NRT); however, when all direct costs were incorporated into the analysis, varenicline was cost-saving. CONCLUSION: The findings from the present study suggest that, compared with the widely used treatment options bupropion and NRT, as well as unaided cessation, varenicline may enhance smoking-cessation treatment outcomes while substantially reducing the overall costs of smoking to the health care system.

Economic impact of delays in listing decisions by provincial drug plans after a positive Common Drug Review recommendation: the case of a smoking-cessation treatment.

Although varenicline (Champix), a smoking-cessation treatment, was recommended for listing by the Common Drug Review (CDR) in 2007, only one CDR-participating drug insurance plan listed it in March 2011 (Saskatchewan). This study estimated the economic impact of delays in the public listing of varenicline in Canada. Using statistical data and peer-reviewed research, social costs and benefits of reimbursing varenicline were estimated. Flows of attempted and successful quitters were projected over a five-year period for three scenarios: immediate listing (2007), one- to four-year listing delays, and no reimbursement. Benefits of public reimbursement of varenicline would have been greatest in the first year ($271 million) and then decreased due to the erosion in smoking prevalence. The current three-year listing delay prevented a projected 17,729 current smokers from quitting, translating into a projected additional lifetime social burden of $700 million. The sizeable opportunity cost of delaying varenicline reimbursement implies broader economic issues for policy makers.

[Effectiveness and safety of varenicline for smoking cessation]. / Effektivität und Sicherheit von Vareniclin zur Raucherentwöhnung.

Smoking is one of the major avoidable risks for mortality and morbidity. Thus developing new strategies for smoking cessation is a crucial medical challenge. Varenicline is an α4ß2 nicotinic acetylcholine receptor partial agonist developed especially for smoking cessation. Several trials proved the efficacy of varenicline and its superiority to other medications for smoking cessation (bupropion and nicotine replacement therapy). Varenicline was associated with severe cardiovascular and neuro-psychiatric side effects. This article discusses the current research data on efficacy and safety of varenicline therapy for smoking cessation.

Cost-effectiveness analysis of varenicline versus existing smoking cessation strategies in Central America and the Caribbean using the BENESCO model.

OBJECTIVES: In Central American countries, the economic burden of tobacco has not been assessed. In Costa Rica, a study demonstrated that tobacco-related diseases represent high costs for the health care system. The aim of this study was to assess the cost-effectiveness of varenicline compared with other existing strategies for smoking cessation within a 10-year time horizon in an adult population cohort from Central American and Caribbean countries using the health care payer's perspective. METHODS: The Benefits of Smoking Cessation on Outcomes simulation model was used for an adult cohort in Costa Rica (n = 2 474 029), Panama (n = 2 249 676), Nicaragua (n = 3 639 948), El Salvador (n = 4 537 803), and the Dominican Republic (n = 6 528 125) (N = 19 429 581). Smoking cessation therapies compared were varenicline (0.5-2 mg/day) versus bupropion (300 mg/day), nicotine replacement therapy (5-15 mg/day), and unaided cessation. Effectiveness measures were: life-years (LYs) gained and quality-adjusted life-years (QALYs) gained. Resource use and cost data were obtained from a country's Ministry of Health and/or Social Security Institutions (2008-2010). The model used a 5% discount rate for costs (expressed in 2010 US$) and health outcomes. Probabilistic sensitivity analyses were conducted and acceptability curves were constructed. RESULTS: Varenicline reduced smoking-related morbidity, mortality, and health care costs in each country included in the study. Accumulatively, mortality in the varenicline arm was reduced by 1190, 1538, and 2902 smoking-related deaths compared with bupropion, nicotine replacement therapy, and unaided cessation, respectively. The net average cost per additional quitter showed that varenicline was cost-saving when compared with competing alternatives. Regarding LYs and QALYs gained in 10 years, varenicline obtained the greatest number of QALYs and LYs in each country, while unaided cessation obtained the fewest. Cost-effectiveness analyses in all 5 countries showed that varenicline was the dominant strategy. Acceptability curves showed that, independent of the willingness to pay, the probability that varenicline is cost-effective was 99% for this region. The results of the probabilistic sensitivity analyses support the robustness of the findings. CONCLUSION: Smoking cessation therapy with varenicline is cost-saving for the Central American and Caribbean countries included. These results could help to reduce the tobacco-related disease burden and align cost-containment policies.

Cost analysis of varenicline versus bupropion, nicotine replacement therapy, and unaided cessation in Nicaragua.

OBJECTIVES: In Nicaragua, 30% of current morbidities are associated with tobacco smoking. Tobacco control policy measures have been initiated in this Central American country; however, the population does not have a complete understanding of the long-term consequences of tobacco use. The aim of this study was to compare the direct medical costs of smoking cessation therapies with varenicline, bupropion, nicotine replacement therapy, and unaided cessation in Nicaragua over 5 time horizons: 2, 5, 10, and 20 years, and lifetime. METHODS: The current annual costs of chronic obstructive pulmonary disease, lung cancer, coronary heart disease, and stroke were estimated based on the current annual incidence for each disease using 1 public hospital database (Hospital Lenin Fonseca, 2010). The Benefits of Smoking Cessation on Outcomes simulation model was used to obtain the projected direct costs for each strategy. An adult cohort (N = 3 639 948) from Nicaragua was used and the assessment was conducted using the health care payer's perspective. Costs were discounted at 5% annually. Probabilistic sensitivity analyses were conducted using a Monte Carlo second-order approach. RESULTS: Varenicline is associated with the highest health care cost-savings compared with the other 3 alternatives at 5, 10, and 20 years, and lifetime. At lifetime, varenicline would result in savings of US$4 545 008, US$5 859 300, and US$11 033 221 when compared with bupropion, nicotine replacement therapy, and unaided cessation, respectively. Varenicline also avoided the highest number of smoking-related deaths in comparison with the alternatives. At year 10, varenicline avoided 96, 124, and 234 more deaths than bupropion, nicotine replacement therapy, and unaided cessation, respectively. The results of probabilistic sensitivity analyses support these findings. CONCLUSION: The use of a smoking cessation therapy with varenicline would generate long-term savings to Nicaragua's health care institutions of > US$11 million in the lifetime time horizon.