Cost-Effectiveness of Lenvatinib in the Treatment of Patients With Unresectable Hepatocellular Carcinomas in Japan: An Analysis Using Data From Japanese Patients in the REFLECT Trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Japan. Prognosis is poor, and until recently sorafenib was the only treatment option available for patients with unresectable disease. Lenvatinib is the first therapy to demonstrate noninferiority to sorafenib. An analysis was conducted using clinical data from Japanese patients in the phase III REFLECT trial to assess the cost-effectiveness of lenvatinib versus sorafenib for first-line treatment of unresectable HCC in Japan. METHODS: A partitioned survival model was implemented adopting the perspective of the Japanese healthcare system, with costs and outcomes modeled over a lifetime horizon and using a discount rate of 2%, as per Japanese guidelines. Population data from the Japanese subpopulation of REFLECT were used to extrapolate outcomes, and costs and resource use were based on Japanese sources. The Japanese tariff was applied to EQ-5D data collected during the REFLECT clinical trial to obtain utility values reflecting the preferences of the Japanese population. RESULTS: Compared with sorafenib, lenvatinib is dominant because it is associated with a reduction in incremental costs of ¥156 799 and incremental quality-adjusted life-years of 0.31. These results were robust to changes in key assumptions, and probabilistic outcomes aligned with deterministic outcomes. CONCLUSION: Given the use of Japan-specific data in the cost-effectiveness model, it is expected that the use of lenvatinib as a first-line treatment in Japan will be associated with cost savings and improved clinical outcomes versus sorafenib for patients with unresectable HCC.

Resource use and direct medical costs of acute respiratory illness in the UK based on linked primary and secondary care records from 2001 to 2009.

BACKGROUND: Previous studies have shown that influenza is associated with a substantial healthcare burden in the United Kingdom (UK), but more studies are needed to evaluate the resource use and direct medical costs of influenza in primary care and secondary care. METHODS: A retrospective observational database study in the UK to describe the primary care and directly-associated secondary care resource use, and direct medical costs of acute respiratory illness (ARI), according to age, and risk status (NCT Number: 01521416). Patients with influenza, ARI or influenza-related respiratory infections during 9 consecutive pre-pandemic influenza peak seasons were identified by READ codes in the linked Clinical Practice Research Datalink (CPRD) and Hospital Episodes Statistics (HES) dataset. The study period was from 21st January 2001 to 31st March 2009. RESULTS: A total of 156,193 patients had ≥1 general practitioner (GP) episode of ARI, and a total of 82,204 patients received ≥1 GP prescription, at a mean of 2.5 (standard deviation [SD]: 3.0) prescriptions per patient. The total cost of GP consultations and prescriptions equated to £462,827 per year per 100,000 patients. The yearly cost of prescribed medication for ARI was £319,732, at an estimated cost of £11,596,350 per year extrapolated to the UK, with 40% attributable to antibiotics. The mean cost of hospital admissions equated to a yearly cost of £981,808 per 100,000 patients. The total mean direct medical cost of ARI over 9 influenza seasons was £21,343,445 (SD: £10,441,364), at £136.65 (SD: £66.85) per case. CONCLUSIONS: Extrapolating to the UK population, for pre-pandemic influenza seasons from 2001 to 2009, the direct medical cost of ARI equated to £86 million each year. More studies are needed to assess the costs of influenza disease to help guide public health decision-making for seasonal influenza in the UK.

Metastatic Renal Cell Cancer: An Analysis of Reimbursement Decisions.

INTRODUCTION: Metastatic renal cell carcinoma is a complex cancer for which several drugs have been developed over the years. More recently, drugs that target the specific cancer cell mutations have been developed for metastatic cell carcinoma. However, even with the recent influx of targeted therapy options, significant unmet needs exist in around half of treated renal cell carcinoma patients following the failure of first-line therapy. The aim of this study was to review the health technology appraisals of renal cell carcinoma treatments in several countries to establish what factors might affect the reimbursement decisions. METHODS: The reimbursement data for 10 drugs in several countries were collated from the health technology assessment bodies for each country. The data included information on clinical trials used in the submission documents for the health technology assessment, the reimbursement decisions and the reasons for those decisions, as well as any specific restrictions for use of any of the included drugs. RESULTS: Of the 10 drugs reviewed, only everolimus received a positive reimbursement decision by all the health technology assessment bodies included in the study. The most common reason for a negative reimbursement decision was lack of demonstration of cost-effectiveness of the drugs. Another frequently cited reason was unproven clinical efficacy and poor impact on overall survival. CONCLUSION: Despite the many treatment guidelines and current treatment options that are available for renal cell carcinoma, there remains an unmet need in patients with metastatic renal cell carcinoma. On the basis of this analysis, the key reason for a drug not obtaining a positive reimbursement decision is due to poor efficacy or uncertainty of the drug's efficacy. FUNDING: Eisai, Inc.

Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan.

BACKGROUND: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. METHODS: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. RESULTS: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY. CONCLUSIONS: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

The role of vaccines and vaccine decision-making to achieve the goals of the Grand Convergence in public health.

On 17 and 18 July 2015, a meeting in Siena jointly sponsored by ADITEC and GlaxoSmithKline (GSK) was held to review the goals of the Global Health 2035 Grand Convergence, to discuss current vaccine evaluation methods, and to determine the feasibility of reaching consensus on an assessment framework for comprehensively and accurately capturing the full benefits of vaccines. Through lectures and workshops, participants reached a consensus that Multi-Criteria-Decision-Analysis is a method suited to systematically account for the many variables needed to evaluate the broad benefits of vaccination, which include not only health system savings, but also societal benefits, including benefits to the family and increased productivity. Participants also agreed on a set of "core values" to be used in future assessments of vaccines for development and introduction. These values include measures of vaccine efficacy and safety, incident cases prevented per year, the results of cost-benefit analyses, preventable mortality, and the severity of the target disease. Agreement on this set of core assessment parameters has the potential to increase alignment between manufacturers, public health agencies, non-governmental organizations (NGOs), and policy makers (see Global Health 2035 Mission Grand Convergence [1]). The following sections capture the deliberations of a workshop (Working Group 4) chartered to: (1) review the list of 24 parameters selected from SMART vaccines (see the companion papers by Timmis et al. and Madhavan et al., respectively) to determine which represent factors (see Table 1) that should be taken into account when evaluating the role of vaccines in maximizing the success of the Global Health 2035 Grand Convergence; (2) develop 3-5 "core values" that should be taken into account when evaluating vaccines at various stages of development; and (3) determine how vaccines can best contribute to the Global Health 2035 Grand Convergence effort.

Cost-effectiveness of seasonal quadrivalent versus trivalent influenza vaccination in the United States: A dynamic transmission modeling approach.

Trivalent inactivated influenza vaccines (IIV3s) protect against 2 A strains and one B lineage; quadrivalent versions (IIV4s) protect against an additional B lineage. The objective was to assess projected health and economic outcomes associated with IIV4 versus IIV3 for preventing seasonal influenza in the US. A cost-effectiveness model was developed to interact with a dynamic transmission model. The transmission model tracked vaccination, influenza cases, infection-spreading interactions, and recovery over 10 y (2012-2022). The cost-effectiveness model estimated influenza-related complications, direct and indirect costs (2013-2014 US$), health outcomes, and cost-effectiveness. Inputs were taken from published/public sources or estimated using regression or calibration. Outcomes were discounted at 3% per year. Scenario analyses tested the reliability of the results. Seasonal vaccination with IIV4 versus IIV3 is predicted to reduce annual influenza cases by 1,973,849 (discounted; 2,325,644 undiscounted), resulting in 12-13% fewer cases and influenza-related complications and deaths. These reductions are predicted to translate into 18,485 more quality-adjusted life years (QALYs) accrued annually for IIV4 versus IIV3. Increased vaccine-related costs ($599 million; 5.7%) are predicted to be more than offset by reduced influenza treatment costs ($699 million; 12.2%), resulting in direct medical cost saving annually ($100 million; 0.6%). Including indirect costs, savings with IIV4 are predicted to be $7.1 billion (5.6%). Scenario analyses predict IIV4 to be cost-saving in all scenarios tested apart from low infectivity, where IIV4 is predicted to be cost-effective. In summary, seasonal influenza vaccination in the US with IIV4 versus IIV3 is predicted to improve health outcomes and reduce costs.

Cost-effectiveness evaluation of quadrivalent influenza vaccines for seasonal influenza prevention: a dynamic modeling study of Canada and the United Kingdom.

BACKGROUND: The adoption of quadrivalent influenza vaccine (QIV) to replace trivalent influenza vaccine (TIV) in immunization programs is growing worldwide, thus helping to address the problem of influenza B lineage mismatch. However, the price per dose of QIV is higher than that of TIV. In such circumstances, cost-effectiveness analyses provide important and relevant information to inform national health recommendations and implementation decisions. This analysis assessed potential vaccine impacts and cost-effectiveness of a country-wide switch from TIV to QIV, in Canada and the UK, from a third-party payer perspective. METHODS: An age-stratified, dynamic four-strain transmission model which incorporates strain interaction, transmission-rate seasonality and age-specific mixing in the population was used. Model input data were obtained from published literature and online databases. In Canada, we evaluated a switch from TIV to QIV in the entire population. For the UK, we considered two strategies: Children aged 2-17 years who receive the live-attenuated influenza vaccine (LAIV) switch to the quadrivalent formulation (QLAIV), while individuals aged > 18 years switch from TIV to QIV. Two different vaccination uptake scenarios in children (UK1 and UK2, which differ in the vaccine uptake level) were considered. Health and cost outcomes for both vaccination strategies, and the cost-effectiveness of switching from TIV/LAIV to QIV/QLAIV, were estimated from the payer perspective. For Canada and the UK, cost and outcomes were discounted using 5 % and 3.5 % per year, respectively. RESULTS: Overall, in an average influenza season, our model predicts that a nationwide switch from TIV to QIV would prevent 4.6 % influenza cases, 4.9 % general practitioner (GP) visits, 5.7 % each of emergency room (ER) visits and hospitalizations, and 6.8 % deaths in Canada. In the UK (UK1/UK2), implementing QIV would prevent 1.4 %/1.8 % of influenza cases, 1.6 %/2.0 % each of GP and ER visits, 1.5 %/1.9 % of hospitalizations and 4.3 %/4.9 % of deaths. Discounted incremental cost-utility ratios of $7,961 and £7,989/£7,234 per quality-adjusted life-year (QALY) gained are estimated for Canada and the UK (UK1/UK2), both of which are well within their respective cost-effectiveness threshold values. CONCLUSIONS: Switching from TIV to QIV is expected to be a cost-effective strategy to further reduce the burden of influenza in both countries.

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study.

OBJECTIVE: Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status. METHODS: This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK. RESULTS: Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively. CONCLUSIONS: Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.

Hidden efficiencies: making completion of the pediatric vaccine schedule more efficient for physicians.

The objective of this work is to demonstrate the potential time and labor savings that may result from increased use of combination vaccinations. The study (GSK study identifier: HO-12-4735) was a model developed to evaluate the efficiency of the pediatric vaccine schedule, using time and motion studies. The model considered vaccination time and the associated labor costs, but vaccination acquisition costs were not considered. We also did not consider any efficacy or safety differences between formulations. The model inputs were supported by a targeted literature review. The reference year for the model was 2012. The most efficient vaccination program using currently available vaccines was predicted to reduce costs through a combination of fewer injections (62%) and less time per vaccination (38%). The most versus the least efficient vaccine program was predicted to result in a 47% reduction in vaccination time and a 42% reduction in labor and supply costs. The estimated administration cost saving with the most versus the least efficient program was estimated to be nearly US $45 million. If hypothetical 6- or 7-valent vaccines are developed using the already most efficient schedule by adding additional antigens (pneumococcal conjugate vaccine and Haemophilus influenzae type b) to the most efficient 5-valent vaccine, the savings are predicted to be even greater. Combination vaccinations reduce the time burden of the childhood immunization schedule and could create the potential to improve vaccination uptake and compliance as a result of fewer required injections.

The potential cost-effectiveness of quadrivalent versus trivalent influenza vaccine in elderly people and clinical risk groups in the UK: a lifetime multi-cohort model.

OBJECTIVE: To estimate the potential cost-effectiveness of quadrivalent influenza vaccine compared with trivalent influenza vaccine in the UK. METHODS: A lifetime, multi-cohort, static Markov model was constructed, with nine age groups each divided into healthy and at-risk categories. Influenza A and B were accounted for separately. The model was run in one-year cycles for a lifetime (maximum age: 100 years). The analysis was from the perspective of the UK National Health Service. Costs and benefits were discounted at 3.5%. 2010 UK vaccination policy (vaccination of people at risk and those aged ≥65 years) was applied. Herd effect was not included. Inputs were derived from national databases and published sources where possible. The quadrivalent influenza vaccine price was not available when the study was conducted. It was estimated at £6.72,15% above the trivalent vaccine price of £5.85. Sensitivity analyses used an incremental price of up to 50%. RESULTS: Compared with trivalent influenza vaccine, the quadrivalent influenza vaccine would be expected to reduce the numbers of influenza cases by 1,393,720, medical visits by 439,852 complications by 167,357, hospitalisations for complications by 26,424 and influenza deaths by 16,471. The estimated base case incremental cost-effectiveness ratio (ICER) was £5,299/quality-adjusted life-year (QALY). Sensitivity analyses indicated that the ICER was sensitive to changes in circulation of influenza virus subtypes and vaccine mismatch; all other parameters had little effect. In 96% of simulations the ICER was <£20,000/QALY. Since this analysis was completed, quadrivalent influenza vaccine has become available in the UK at a list price of £9.94. Using this price in the model, the estimated ICER for quadrivalent compared with trivalent vaccination was £27,378/QALY, still within the NICE cost-effectiveness threshold (£20,000-£30,000). CONCLUSIONS: Quadrivalent influenza vaccine could reduce influenza disease burden and would be cost-effective compared with trivalent influenza vaccine in elderly people and clinical risk groups in the UK.

Cost-effectiveness analysis of universal influenza vaccination with quadrivalent inactivated vaccine in the United States.

To address influenza B lineage mismatch and co-circulation, several quadrivalent inactivated influenza vaccines (IIV4s) containing two type A strains and both type B lineages have recently been approved in the United States. Currently available trivalent inactivated vaccines (IIV3s) or trivalent live attenuated influenza vaccines (LAIV3s) comprise two influenza A strains and one of the two influenza B lineages that have co-circulated in the United States since 2001. The objective of this analysis was to evaluate the cost-effectiveness of a policy of universal vaccination with IIV4 vs. IIV3/LAIV3 during 1 year in the United States. On average per influenza season, IIV4 was predicted to result in 30,251 fewer influenza cases, 3512 fewer hospitalizations, 722 fewer deaths, 4812 fewer life-years lost, and 3596 fewer quality-adjusted life-years (QALYs) lost vs. IIV3/LAIV3. Using the Fluarix Quadrivalent(TM) (GlaxoSmithKline) prices and the weighted average IIV3/LAIV3 prices, the model predicts that the vaccination program costs would increase by $452.2 million, while direct medical and indirect costs would decrease by $111.6 million and $218.7 million, respectively, with IIV4. The incremental cost-effectiveness ratio (ICER) comparing IIV4 to IIV3/LAIV3 is predicted to be $90,301/QALY gained. Deterministic sensitivity analyses found that influenza B vaccine-matched and mismatched efficacies among adults aged ≥65 years had the greatest impact on the ICER. Probabilistic sensitivity analysis showed that the cost per QALY remained below $100,000 for 61% of iterations. In conclusion, vaccination with IIV4 in the US is predicted to reduce morbidity and mortality. This strategy is also predicted to be cost-effective vs. IIV3/LAIV3 at conventional willingness-to-pay thresholds.

Influenza-related health care utilization and productivity losses during seasons with and without a match between the seasonal and vaccine virus B lineage.

OBJECTIVE: To assess and compare direct medical costs (incurred by payers) and indirect productivity losses (incurred by employers) associated with influenza seasons with matched or mismatched circulating and vaccine containing influenza B lineages. METHODS: A retrospective analysis, using two MarketScan databases, for the years 2000-2009. Each influenza season was categorized as matched or mismatched after comparing that season's circulating influenza B lineage and the vaccine influenza B lineage. Patients selected had at least one diagnosis claim for influenza (ICD-9-CM code 487.xx [influenza] or 488.1 [H1N1]) during an influenza season. We assessed the incidence of influenza (overall and influenza B), influenza-related medical utilization and associated costs, and productivity losses for each season. RESULTS: The four matched seasons had lower average influenza incidence (overall incidence per 100,000 plan members: 509; 95% confidence interval [CI]: 505-512) than the five mismatched seasons (748; 95% CI: 745-751). The mismatched seasons had lower influenza B incidence (average incidence per 100,000 plan members: 126; 95% CI: 125-128) than the matched seasons (165; 95% CI: 163-167). The average, per-patient, total influenza-related medical costs in the mismatched seasons ($300.83; range: $245.38-$371.58) were approximately $61.00 higher than in the matched seasons ($239.43; range: $201.49-$264.01). The mismatched seasons had greater average per-patient, influenza-related productivity-loss costs than the matched seasons (mean: $237.31 vs. $175.10). CONCLUSION: CDC data showed that influenza A was the predominant circulating strain during seasons in which the circulating influenza B lineage did not match the vaccine influenza B lineage. This resulted in lower influenza B incidence during the mismatched seasons. However, the average, per-patient, influenza-related direct medical costs and indirect productivity losses were higher during the mismatched seasons. Additional research is required to determine if these higher costs can be attributed to influenza B infections and if the influenza severity varies during mismatched seasons.

An approximation of herd effect due to vaccinating children against seasonal influenza - a potential solution to the incorporation of indirect effects into static models.

BACKGROUND: Indirect herd effect from vaccination of children offers potential for improving the effectiveness of influenza prevention in the remaining unvaccinated population. Static models used in cost-effectiveness analyses cannot dynamically capture herd effects. The objective of this study was to develop a methodology to allow herd effect associated with vaccinating children against seasonal influenza to be incorporated into static models evaluating the cost-effectiveness of influenza vaccination. METHODS: Two previously published linear equations for approximation of herd effects in general were compared with the results of a structured literature review undertaken using PubMed searches to identify data on herd effects specific to influenza vaccination. A linear function was fitted to point estimates from the literature using the sum of squared residuals. RESULTS: The literature review identified 21 publications on 20 studies for inclusion. Six studies provided data on a mathematical relationship between effective vaccine coverage in subgroups and reduction of influenza infection in a larger unvaccinated population. These supported a linear relationship when effective vaccine coverage in a subgroup population was between 20% and 80%. Three studies evaluating herd effect at a community level, specifically induced by vaccinating children, provided point estimates for fitting linear equations. The fitted linear equation for herd protection in the target population for vaccination (children) was slightly less conservative than a previously published equation for herd effects in general. The fitted linear equation for herd protection in the non-target population was considerably less conservative than the previously published equation. CONCLUSIONS: This method of approximating herd effect requires simple adjustments to the annual baseline risk of influenza in static models: (1) for the age group targeted by the childhood vaccination strategy (i.e. children); and (2) for other age groups not targeted (e.g. adults and/or elderly). Two approximations provide a linear relationship between effective coverage and reduction in the risk of infection. The first is a conservative approximation, recommended as a base-case for cost-effectiveness evaluations. The second, fitted to data extracted from a structured literature review, provides a less conservative estimate of herd effect, recommended for sensitivity analyses.

Employer-incurred health care costs and productivity losses associated with influenza.

The primary objective of this study was to assess trends in employer expenditures for both direct medical costs and indirect productivity losses associated with influenza. A retrospective analysis was performed using two of the MarketScan family of databases for 2005-2009. Patients with at least one diagnosis claim for influenza during an influenza season were selected. We estimated seasonal incidence of influenza in the employed population from the MarketScan Commercial Claims and Encounters database. Health care utilization and costs and productivity losses were assessed during the 21-d period following the influenza diagnosis date. Compared with the 2005-2006 season (493 per 100,000 plan members), influenza incidence increased during the 2006-2007 (598 per 100,000 plan members) and 2007-2008 (1,142 per 100,000 plan members) seasons and had a dramatic increase during the pandemic season of 2008-2009 (1,715 per 100,000 plan members) . The total influenza-related employer spending per 100,000 plan members also increased by over 400% during the 2008-2009 influenza season [$623,248; confidence interval (CI]):$601,518-$644,991], compared with 2005-2006 ($145,834; 95% CI: $135,067-$156,603). The primary drivers of the increased costs were emergency room, outpatient and inpatient visits. Total costs associated with influenza-related missed work time per 100,000 plan members increased over 4-fold from $26,479 in the 2005-2006 influenza season to $122,811 in 2008-2009. Overall, as expected, considerably higher direct and indirect costs were observed during the 2008-2009 influenza pandemic season than during other influenza seasons. In recent years, the influenza-related employer burden has increased considerably. In future, employers may need efficient resource allocation in order to address the productivity losses and increasing direct medical costs associated with increased influenza incidence. One of the strategies that employers may consider is increasing influenza vaccination rates among employees, which likely will help lower the influenza incidence and the associated downstream direct and indirect costs.

Cost effectiveness of quetiapine in patients with acute bipolar depression and in maintenance treatment after an acute depressive episode.

BACKGROUND: Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs. OBJECTIVE: The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy). METHODS: Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs. RESULTS: For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained. CONCLUSION: Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.