Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective.

OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m2, and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis.

Cost-Effectiveness Analysis of Smoking Cessation Interventions in the United Kingdom Accounting for Major Neuropsychiatric Adverse Events.

OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom. METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information. RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose. CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.

Valor social de los medicamentos para dejar de fumar. Opiniones respecto a su financiación / Social value of medicines to stop smoking.Opinions regarding its financing

Las medidas de la OMS para controlar el tabaquismo han disminuido su prevalencia, pero aumentando las diferencias entre grupos sociales. Facilitar el acceso a los medicamentos, para dejar de fumar, a los desfavorecidos disminuye la prevalencia sin aumentar diferencias. Recientemente se ha aprobado la financiación de vareniclina y bupropion pero esa medida es susceptible de ser eliminada (ya ha ocurrido con otros medicamentos) o ampliada a la TSN y bupropion. OBJETIVO: 1) Conocer el uso del tabaco según el estatus socioeconómico. 2) Conocer la opinión de la población respecto a la financiación según el estatus socioeconómico y uso del tabaco. METODO: Estudio descriptivo poblacional. RESULTADOS: Aumenta el consumo de tabaco al disminuir el estatus. El 64,3% está a favor de la financiación. Exceptuando a los individuos sin estudios, disminuye la opinión favorable al aumentar el nivel académico. Aumenta dicha opinión al aumentar la relación con el tabaco, mínima en los no fumadores (52,6%) y máxima en fumadores diarios (79,8%). DISCUSIÓN: El resultado coincide con otros estudios, pero no con las consideraciones de un informe de 2011 de la Agencia de Evaluación de las Tecnologías Sanitarias. La no coincidencia pudiera ser una evolución de la opinión de la población, que pasa de acentuar el problema en la responsabilidad del consumidor a considerar una etiología más compleja que no solo depende del individuo. Dado el gran apoyo a la medida, ésta no debería depender, en el futuro, de situaciones políticas o económicas y debería ampliarse a TSN y bupropion

WHO's measures to control smoking have facilitated the decrease in its prevalence but increasing the differences between social groups. Facilitating the access to medicines, to quit smoking, to the most disadvantaged, decreases the prevalence without increasing the differences between groups. Recently, the financing of varenicline and bupropion has been approved but that measure could be eliminated (it has already happened with other medications) or extended to the TSN and bupropion. OBJETIVE: 1) Knowing the use of tobacco according to socioeconomic status, 2) Knowing the opinion of the population regarding the financing according to the socioeconomic status and tobacco use. METHOD: Population descriptive study. RESULTS: Increases tobacco consumption by decreasing status. 64.3% are in favour of funding. Except for individuals without studies, the favorable opinion of the measure decreases as the academic level increases. This opinion increases as the relationship with tobacco increases, being minimal in non-smokers (52.6%) and maximum in daily smokers (79.8%). DISCUSSION: The result coincides with other studies, but not with the considerations of a 2011 report by the Health Technology Assessment Agency. The non-coincidence could be an evolution of the opinion of the population, which goes from accentuating the problem in the responsibility of the consumer to considering a more complex aetiology that not only depends on the individual. Given the great support for the measure, it should not depend on political or economic situations in the future and should be extended to TSN and bupropion

Cost-utility analysis of smoking cessation to prevent operative complications following elective abdominal colon surgery.

BACKGROUND: Smoking is a known risk factor for postoperative complications after colectomy. Using the perspective of the provider, this study evaluated the cost-effectiveness of the pharmacologic interventions for smoking cessation. METHODS: A decision tree model was constructed to represent a provider's decision to provide either bupropion, nicotine replacement therapy, varenicline, or no cessation therapy to all patients presenting for elective colectomy. Incremental cost per quality-adjusted life year (QALY) was the primary outcome. RESULTS: The base case analysis suggests that bupropion is cost-effective with an incremental cost-effectiveness ratio of approximately $75,000 per QALY. Sensitivity analyses established ranges for which each medication might be cost-effective and dominant compared to offering no cessation therapy. CONCLUSIONS: From a provider perspective, offering bupropion for smoking cessation to patients scheduled for elective colon resection is cost-effective. Furthermore, these results provide benchmarks to inform providers about whether targeted, short-term smoking cessation therapies represent good value in colectomies.

A health economic model to assess the cost-effectiveness of OPTIFAST for the treatment of obesity in the United States.

OBJECTIVES: Obesity is associated with high direct medical costs and indirect costs resulting from productivity loss. The high prevalence of obesity generates a justified need to identify cost-effective weight loss approaches from a payer's perspective. Within the variety of weight management techniques, OPTIFAST is a clinically recognized and scientifically proven total meal replacement Low Calorie Diet that provides meaningful results in terms of weight loss and reduction in comorbidities. The objective of this study is assess potential cost-savings of the OPTIFAST program in the US, as compared to "no intervention" and pharmacotherapy. METHODS: An event-driven decision analytic model was used to estimate payer's cost-savings from reimbursement of the 1-year OPTIFAST program over 3 years in the US. The analysis was performed for the broad population of obese persons (BMI >30 kg/m2) undergoing the OPTIFAST program vs liraglutide 3 mg, naltrexone/bupropion and vs "no intervention". The model included the risk of complications related to increased BMI. Data sources included published literature, clinical trials, official US price/tariff lists, and national population statistics. The primary perspective was that of a US payer; costs were provided in 2016 US dollars. RESULTS: OPTIFAST leads over a period of 3 years to cost-savings of USD 9,285 per class I and II obese patient (BMI 30-39.9 kg/m2) as compared to liraglutide and USD 685 as compared to naltrexone/bupropion. In the same time perspective, the OPTIFAST program leads to a reduction of cost of obesity complications of USD 1,951 as compared to "no intervention", with the incremental cost-effectiveness ratio of USD 6,475 per QALY. Scenario analyses also show substantial cost-savings in patients with class III obesity (BMI ≥ 40.0 kg/m2) and patients with obesity (BMI = 30-39.9 kg/m2) and type 2 diabetes vs all three previous comparators and bariatric surgery. CONCLUSIONS: Reimbursing OPTIFAST leads to meaningful cost-savings for US payers as compared with "no intervention" and liraglutide and naltrexone/bupropion in obese patients. Similar results can be expected in matching healthcare settings of other countries. Moreover, OPTIFAST has additional clinical and economic advantages through very low complication and adverse events rates.

Comparing Cost-Effectiveness of Aripiprazole Augmentation With Other "Next-Step" Depression Treatment Strategies: A Randomized Clinical Trial.

OBJECTIVE: To compare the cost-effectiveness of 3 common alternate treatments for depression. METHODS: The cost-effectiveness analysis was conducted as part of a randomized clinical trial, the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) trial, in which patients were randomized from December 2012 to May 2015 and followed for 12 weeks in 35 Veterans Affairs medical centers. Depression diagnosis was based on ICD-9 codes. Patients were randomized to standard antidepressant therapy augmented with aripiprazole, standard antidepressant therapy augmented with bupropion, or switch to bupropion. Remission was measured using the 16-item Quick Inventory of Depressive Symptomatology-Clinican Rated. Outcomes included the incremental cost-effectiveness ratio (ICER) comparing costs per remission and costs per quality-adjusted life-year (QALY) with 12 weeks as the time horizon using the health care sector perspective. RESULTS: The mean age of participants enrolled in the trial (N = 1,522) was 54 years, and participants were predominantly male. The rate of remission at 12 weeks was highest for the aripiprazole augmentation arm (29%), followed by bupropion augmentation (27%), and lowest for switching to bupropion (22%). Switching to bupropion was strongly dominated by bupropion augmentation at an ICER of -$640/remission (95% CI, -$5,770 to $3,008). The ICER for the aripiprazole augmentation versus switching to bupropion was $1,074/remission (95% CI, $47 to $5,022), and the ICER for aripiprazole augmentation versus bupropion augmentation was $5,094/remission (95% CI, -$34,027 to $32,774). There were no significant differences in QALYs, mental health care costs, employment, or other work and social adjustment outcomes between treatment groups. CONCLUSIONS: In treatment of depression with less than optimal response, augmentation with either aripiprazole or bupropion was cost-effective relative to switching to bupropion. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01421342.

Using PICO Methodology to Answer Questions About Smoking in COPD Patients. / Preguntas y respuestas relacionadas con tabaquismo en pacientes con EPOC. Aplicación de metodología con formato PICO.

The ALAT and SEPAR Treatment and Control of Smoking Groups have collaborated in the preparation of this document which attempts to answer, by way of PICO methodology, different questions on health interventions for helping COPD patients to stop smoking. The main recommendations are: (i)moderate-quality evidence and strong recommendation for performing spirometry in COPD patients and in smokers with a high risk of developing the disease, as a motivational tool (particularly for showing evidence of lung age), a diagnostic tool, and for active case-finding; (ii)high-quality evidence and strong recommendation for using intensive dedicated behavioral counselling and drug treatment for helping COPD patients to stop smoking; (iii)high-quality evidence and strong recommendation for initiating interventions for helping COPD patients to stop smoking during hospitalization with improvement when the intervention is prolonged after discharge, and (iv)high-quality evidence and strong recommendation for funding treatment of smoking in COPD patients, in view of the impact on health and health economics.

Cost-Effective Drug Switch Options After Unsuccessful Treatment With an SSRI for Depression.

OBJECTIVE: Multiple treatment options are available for patients who do not respond to initial treatment for major depressive disorder. Previous results show that bupropion, sertraline, and venlafaxine are comparable in terms of therapeutic effectiveness following unsuccessful treatment with citalopram. In this study, we extended these results by incorporating costs of treatment to determine if one option was more cost-effective relative to others. METHODS: In the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) trial, 727 patients were randomly assigned to a switch drug treatment during level 2; 239 (33%) were assigned to bupropion, 238 (33%) to sertraline, and 250 (34%) to venlafaxine. For each study medication, the total costs included the costs of the medication, other concomitant medication and antidepressants, and health care facility utilization. Effectiveness was measured as remission and response. Cost-effectiveness was assessed as net health benefits. Stochastic analysis was performed by using the bootstrapping method. RESULTS: During level 2, mean medication costs were significantly higher for venlafaxine than for bupropion and sertraline ($968, $607, and $703, respectively). There were no significant differences among the switch medications in costs for other medications and health care facility utilization. Although the total costs were significantly different for the three medications (p=.025), none of the pairwise differences between medications were significant. Also, after jointly estimating costs and effects, the analyses found that net health benefits were not significantly different among the three drugs. CONCLUSIONS: After unsuccessful treatment with citalopram, the switch options of bupropion, sertraline, and venlafaxine were not significantly different from each other in terms of cost-effectiveness.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland.

BACKGROUND: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin-norepinephrine reuptake inhibitors. METHODS: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. RESULTS: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. CONCLUSION: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Analysis of Driving Factors of Willingness to Use and Willingness to Pay for Existing Pharmacological Smoking Cessation Aids Among Young and Middle-Aged Adults in Germany.

BACKGROUND: Smoking cessation is a challenging task with a high risk of relapse. Depending on the choice of medication and duration of therapy, the costs of using a smoking cessation aid can be high. Additionally, these costs are not covered by health insurance in Germany. Information on willingness to use (WTU) and willingness to pay (WTP) for smoking cessation aids is valuable for developing different smoking cessation strategies. OBJECTIVES: The study analyses WTU and WTP for three pharmacological smoking cessation aids (nicotine replacement therapy (NRT), bupropion and varenicline) among young and middle-aged adults in Germany and attempts to determine their major driving factors. METHODS: Two cross-sectional internet-based surveys of smokers over 18 years of age were conducted in 2014 and 2015 in Germany. Respondents were asked about smoking-related issues and WTU and WTP for each therapy. The contingent valuation method with payment cards was used to measure WTP. Descriptive statistics, logistical regression and accelerated failure-time regression models were performed. RESULTS: The total sample size is 505. Half of the respondents are willing to use NRT and one-third are willing to use bupropion and/or varenicline. WTU induces positive WTP; however, the magnitude of WTP is beneath the market price. WTU significantly increases with a higher addiction level and if smokers have previously heard about the therapy. CONCLUSION: This study indicates different points to be considered for policy development. Promotion information and improving awareness about medication aids might increase WTU, and development of monetary incentives for young smokers could create a better chance for successful smoking cessation.

Medicaid Tobacco Cessation: Big Gaps Remain In Efforts To Get Smokers To Quit.

Medicaid enrollees are about twice as likely as the general US population to smoke tobacco: 32 percent of people in the program identify themselves as smokers. This article provides the first data about the effectiveness of state Medicaid programs in promoting smoking cessation. Our analysis of Medicaid enrollees' use of cessation medications found that about 10 percent of current smokers received cessation medications in 2013. Every state Medicaid program covers cessation benefits, but the use of these medications varies widely, with the rate in Minnesota being thirty times higher than that in Texas. Most states could increase their efforts to help smokers quit, working with public health agencies, managed care plans, and others. In 2013 Medicaid spent $103 million on cessation medications-less than 0.25 percent of the estimated cost to Medicaid of smoking-related diseases. Additionally, states that have not expanded Medicaid eligibility in the wake of the Affordable Care Act have higher smoking prevalence and lower utilization rates of cessation medication, compared to expansion states. Given these factors, nonexpansion states will have a greater public health burden related to smoking. Medicaid and public health agencies should work together to make smoking cessation a priority for Medicaid beneficiaries.

Higher Adherence During Reimbursement of Pharmacological Smoking Cessation Treatments.

INTRODUCTION: In the Netherlands, pharmacologic Smoking Cessation Treatments (pSCTs) were reimbursed in 2011. In 2012 the reimbursement was discontinued. As of 2013, pSCTs were again reimbursed, provided they are accompanied by behavioral counseling. The aim of this article is to assess the impact of changes in reimbursement policy on use of-and adherence to-pSCTs. METHODS: A retrospective dispensing database analysis was performed on real-world observational data (2010-2013) from the Netherlands. Data on use and adherence was collected, in patients who were dispensed bupropion or varenicline in community pharmacies for the first time. Using the InterActionDataBase (iadb.nl), adherence per patient that initiated varenicline or bupropion was calculated by adding up all dispenses between initiation of the therapy and the 120 days thereafter. Good adherence was defined as using minimal 80% of the recommended duration and intensity of use. RESULTS: The prevalence of patients initiating pSCTs was stable at 0.4 per 1000 inhabitants per quarter during 2010. In 2011, the prevalence was on average 0.7, with peaks in the first (0.8 per 1000) and fourth (1.0 per 1000) quarters of 2011. In 2012, the prevalence was stable again at 0.3. In 2013, prevalence was on average 0.4, with a small peak in the first quarter. Adherence was 15.4% in 2010 versus 20.1% in 2011 (P = .002). In 2012, adherence was 13.9%, compared with 18.9% in 2013 (P = .008). CONCLUSIONS: Not only the likelihood of initiating pSCTs, but also the extent of adherence to these treatments, although generally low, seems higher during reimbursement.

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.).

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.

Action to stop smoking in suspected tuberculosis (ASSIST) in Pakistan: a cluster randomized, controlled trial.

BACKGROUND: Tobacco use is responsible for a large proportion of the total disease burden from tuberculosis. Pakistan is one of the 10 high-burden countries for both tuberculosis and tobacco use. OBJECTIVE: To assess the effectiveness of a behavioral support intervention and bupropion in achieving 6-month continuous abstinence in adult smokers with suspected pulmonary tuberculosis. DESIGN: Cluster randomized, controlled trial. (Current Controlled Trials: ISRCTN08829879) SETTING: Health centers in the Jhang and Sargodha districts in Pakistan. PATIENTS: 1955 adult smokers with suspected tuberculosis. INTERVENTION: Health centers were randomly assigned to provide 2 brief behavioral support sessions (BSS), BSS plus 7 weeks of bupropion therapy (BSS+), or usual care. MEASUREMENTS: The primary end point was continuous abstinence at 6 months after the quit date and was determined by carbon monoxide levels in patients. Secondary end points were point abstinence at 1 and 6 months. RESULTS: Both treatments led to statistically significant relative risks (RRs) for abstinence compared with usual care (RR for BSS+, 8.2 [95% CI, 3.7 to 18.2]; RR for BSS, 7.4 [CI, 3.4 to 16.4]). Equivalence between the treatments could not be established. In the BSS+ group, 275 of 606 patients (45.4% [CI, 41.4% to 49.4%]) achieved continuous abstinence compared with 254 of 620 (41.0% [CI, 37.1% to 45.0%]) in the BSS group and 52 of 615 (8.5% [CI, 6.4% to 10.9%]) in the usual care group. There was substantial heterogeneity of program effects across clusters. LIMITATIONS: Imbalances in the urban and rural proportions and smoking habits among treatment groups, and inability to confirm adherence to bupropion treatment and validate longer-term abstinence or the effect of smoking cessation on tuberculosis outcomes. CONCLUSION: Behavioral support alone or in combination with bupropion is effective in promoting cessation in smokers with suspected tuberculosis. PRIMARY FUNDING SOURCE: International Development Research Centre.

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.

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.

Systematic review of the cost-effectiveness of varenicline vs. bupropion for smoking cessation.

The purpose of this systematic review was to review the cost-effectiveness of first-line non-nicotine therapies (varenicline and bupropion SR) for smoking cessation, identify differences in the models used and their conclusions of cost-effectiveness, and to determine which variables, if any, impact conclusions of cost-effectiveness. A systematic literature search was conducted in MEDLINE, PsychINFO, the National Health Service Economic Evaluation Database, the Health Technology Database and the Tufts Cost-effectiveness Analysis Registry from the earliest possible date through May 2011. To be included, studies had to compare cost-effectiveness of varenicline to bupropion using either a Markov model or discrete event simulation and be published as a full text manuscript in English or Spanish. Study selection and data extraction were done in duplicate with disagreement resolved through discussion. Data regarding the model characteristics, results and conclusions were extracted as were details to assess the quality of the study. Model characteristics and cost-effectiveness results were compared across studies and summarised qualitatively. Ten unique studies were included, all of which were Markov models. Eight studies used the Benefits of Smoking Cessation on Outcomes (BENESCO) model and all found varenicline to dominate bupropion. The two non-BENESCO models found varenicline to be cost-effective. Conclusions regarding the cost-effectives were changed upon sensitivity analysis with the following variables: time horizon, cost of bupropion, efficacy of either drug, age and the incidence of smoking related disease. Varenicline dominated bupropion in most cost-effectiveness models. However, applicability of models to clinical practice and variables which changed conclusion of cost-effectiveness should be considered in the interpretation of results.