Cost-Effectiveness Analysis of Adjuvant Olaparib Versus Watch and Wait in the Treatment of Germline BRCA1/2-Mutated, High-Risk, HER2-Negative Early Breast Cancer in Sweden.

INTRODUCTION: This study evaluated the cost effectiveness of adjuvant olaparib versus watch and wait (WaW) in patients with germline breast cancer susceptibility gene 1/2 (gBRCA1/2)-mutated, high-risk, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC), previously treated with neoadjuvant or adjuvant chemotherapy, from a Swedish healthcare perspective. METHODS: A five-state (invasive disease-free survival [IDFS], non-metastatic breast cancer [non-mBC], early-onset mBC, late-onset mBC, death) semi-Markov state transition model with a lifetime horizon was developed. Transition probabilities were informed by data from the Phase III OlympiA trial, supplemented with data from additional studies in BRCA-mutated, HER2-negative mBC. Health state utilities were derived via mapping of OlympiA data and supplemented by literature estimates. Treatment, adverse events and other medical costs were extracted from publicly available Swedish sources. Incremental cost per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Costs and outcomes were discounted at 3% annually. One-way deterministic and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: Over a lifetime horizon, adjuvant olaparib was associated with an additional 1.50 LYs and 1.22 QALYs, and incremental cost of 471,156 Swedish krona (SEK) versus WaW (discounted). The resulting ICER was 385,183SEK per QALY gained for olaparib versus WaW. ICERs remained below 1,000,000SEK across a range of scenarios, and were consistent across subgroups (hormone receptor [HR]-positive/HER2-negative and triple-negative breast cancer [TNBC]). In PSA, the probability of olaparib being cost effective at 1,000,000SEK per QALY was 99.8%. CONCLUSIONS: At list price, adjuvant olaparib is a cost-effective alternative to WaW in patients with gBRCA1/2-mutated, high-risk, HER2-negative eBC in Sweden.

Cost-Effectiveness Analysis of Fulvestrant 500 mg in Endocrine Therapy-Naïve Postmenopausal Women with Hormone Receptor-Positive Advanced Breast Cancer in the UK.

INTRODUCTION: The selective estrogen receptor degrader fulvestrant is approved for the first-line treatment of postmenopausal patients with hormone receptor-positive (HR+), locally advanced or metastatic breast cancer who have not received prior endocrine therapy. We evaluated the cost-effectiveness of fulvestrant versus comparator treatments in endocrine therapy-naïve patients with locally advanced or metastatic breast cancer. METHODS: A three-health-state (progression free, progressed disease, and death) partitioned survival model from the UK National Health Service and Personal Social Services perspective was developed to extrapolate study data for the cumulative probability of progression-free survival and overall survival to a lifetime (30-year) horizon. Relative comparator data were derived from a systematic literature review-informed network meta-analysis. Sensitivity analyses were applied to assess the impact of uncertainty in the parameter input values on the results. RESULTS: Over a lifetime horizon (30 years), the incremental cost (British pounds sterling) per patient associated with fulvestrant treatment was £18,867 versus anastrozole, £23,097 versus letrozole, and £17,131 versus tamoxifen, with incremental quality-adjusted life-years of 0.55, 0.77, and 0.76, respectively, and incremental cost-effectiveness ratios of £34,109, £29,827, and £22,532, respectively. The largest difference in costs between fulvestrant and the comparators was related to treatment costs. CONCLUSIONS: Results suggest that fulvestrant could potentially be a cost-effective option compared with other endocrine monotherapies (anastrozole, letrozole, and tamoxifen) for treating endocrine therapy-naïve, postmenopausal women with HR+, locally advanced or metastatic breast cancer.

Weight change patterns and healthcare costs in patients with newly-diagnosed type-2 diabetes in Sweden.

AIMS: To describe weight-change pathways in patients with type 2 diabetes (T2D) and associated healthcare costs using repeated BMI measurements and healthcare utilization data. METHODS: Patients with newly-diagnosed T2D with body mass index (BMI, kg/m2) at diagnosis and subsequent measures at year 1-3 were identified. Based on three-year BMI change, patients were assigned to one of 27 BMI change pathways defined by annual BMI change: BMI↗ (≥1 BMI unit increase), BMI→ (<1 BMI unit change), and BMI↘ (≥1 BMI unit decrease). Mean annual and three-year cumulative healthcare costs were estimated for each pathway by combining Swedish unit costs with resource use from primary care and national patient registers. RESULTS: Cohort consisted of 15,819 patients; 44% women, mean age of 61 years, HbA1c of 6.7% (50mmol/mol), BMI of 30.6kg/m2. Most common BMI pathways (mean costs): BMI→→→ (€5,311), BMI↘→→ (€5,461), and BMI→→↘ (€6,281). General trends: BMI→→→ linked to lowest, BMI↗→↗ linked to highest costs. CONCLUSION: In patients with newly-diagnosed T2D, weight stability was the most common BMI change pattern over 3 years and associated with lowest healthcare costs. Relationship between weight change and healthcare costs appears complex warranting further investigation.

Economic Evaluation of Fulvestrant 500 mg Compared to Generic Aromatase Inhibitors in Patients with Advanced Breast Cancer in Sweden.

OBJECTIVES: In Sweden, breast cancer (BC) represents 30% of newly diagnosed cancers and is the most common cancer in women. For hormone-dependent BC, endocrine therapies varying in efficacy and price are available. The aim of this study is to assess the cost effectiveness of fulvestrant 500 mg as a second-line hormonal therapy for postmenopausal women with estrogen receptor-positive metastatic or locally advanced BC versus letrozole, anastrozole, and exemestane in Sweden. METHODS: A three-state (pre-progression, post-progression, and death) partitioned-survival model was used to estimate progression-free (PFS) and overall survival (OS) by extrapolating trial results beyond the trial period to capture costs and benefits over a lifetime perspective. The comparative effectiveness was sourced from a network meta-analysis. The evaluation was conducted from a Swedish national payer perspective; costs, resource use, and quality of life were based on published sources and expert opinion. RESULTS: Compared to anastrozole, letrozole, and exemestane the incremental cost-effectiveness ratios (ICERs) were €33,808, €33,883, and €49,225 per QALY with incremental costs of €13,283, €14,986, and €13,862, and incremental QALYs of 0.393, 0.442, and 0.282, respectively. Incremental cost per life-year (LY) gained €21,312 (incremental LY of 0.623), €20,338 (incremental LY of 0.737), and €27,854 (incremental LY of 0.498) for respective comparators. Applying the upper and lower credible intervals for PFS/OS from the meta-analysis had the greatest effect on the ICER in the sensitivity analysis. The results were relatively stable when varying other parameters. CONCLUSIONS: Our results indicate that fulvestrant 500 mg may be a cost-effective alternative to aromatase inhibitors at a threshold of €100,000/QALY.

Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes: A long-term follow-up in clinical practice.

AIMS: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. METHODS: Patients newly initiated on insulin (n=2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. RESULTS: The total mean annual healthcare cost increased from €1656 per patient 2 years before insulin initiation to €3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was €13,823 in the insulin group compared to €9989 in the NIAD group. CONCLUSIONS: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line.

Cost-effectiveness of dapagliflozin (Forxiga®) added to metformin compared with sulfonylurea added to metformin in type 2 diabetes in the Nordic countries.

AIMS: The aim of this study was to assess the long-term cost-effectiveness of dapagliflozin (Forxiga(®)) added to metformin, compared with sulfonylurea (SU) added to metformin, in Nordic Type 2 diabetes mellitus (T2DM) patients inadequately controlled on metformin. METHODS: Data from a 52-week clinical trial comparing dapagliflozin and SU in combination with metformin was used in a Cardiff simulation model to estimate long term diabetes-related complications in a cohort of T2DM patients. Costs and QALYs were calculated from a healthcare provider perspective and estimated over a patient's lifetime. RESULTS: Compared with metformin+SU, the cost per QALY gained with dapagliflozin+metformin was €7944 in Denmark, €5424 in Finland, €4769 in Norway, and €6093 in Sweden. Metformin+dapagliflozin was associated with QALY gains ranging from 0.236 in Norway to 0.278 in Sweden and incremental cost ranging from €1125 in Norway to €1962 in Denmark. Results were robust across both one-way and probabilistic sensitivity analyses. Results were driven by weight changes associated with each treatment. CONCLUSIONS: Results indicate that metformin+dapagliflozin is associated with gains in QALY compared with metformin+SU in Nordic T2DM patients inadequately controlled on metformin. Dapagliflozin treatment is a cost-effective treatment alternative for Type 2 diabetes in all four Nordic countries.

Analyzing overall survival in randomized controlled trials with crossover and implications for economic evaluation.

BACKGROUND: Offering patients in oncology trials the opportunity to cross over to active treatment at disease progression is a common strategy to address ethical issues associated with placebo controls but may lead to statistical challenges in the analysis of overall survival and cost-effectiveness because crossover leads to information loss and dilution of comparative clinical efficacy. OBJECTIVES: We provide an overview of how to address crossover, implications for risk-effect estimates of survival (hazard ratios) and cost-effectiveness, and how this influences decisions of reimbursement agencies. Two case studies using data from two phase III sunitinib oncology trials are used as illustration. METHODS: We reviewed the literature on statistical methods for adjusting for crossover and recent health technology assessment decisions in oncology. RESULTS: We show that for a trial with a high proportion of crossover from the control arm to the investigational arm, the choice of the statistical method greatly affects treatment-effect estimates and cost-effectiveness because the range of relative mortality risk for active treatment versus control is broad. With relatively frequent crossover, one should consider either the inverse probability of censoring weighting or the rank-preserving structural failure time model to minimize potential bias, with choice dependent on crossover characteristics, trial size, and available data. A large proportion of crossover favors the rank-preserving structural failure time model, while large sample size and abundant information about confounding factors favors the inverse probability of censoring weighting model. When crossover is very infrequent, methods yield similar results. CONCLUSIONS: Failure to correct for crossover may lead to suboptimal decisions by pricing and reimbursement authorities, thereby limiting an effective drug's potential.

The societal cost of bipolar disorder in Sweden.

PURPOSE: There is a lack of comprehensive cost-of-illness studies in bipolar disorder, in particular studies based on patient-level data. The purpose of this study was to estimate the societal cost of bipolar disorder and to relate costs to disease severity, depressive episodes, hospitalisation and patient functioning. METHODS: Retrospective resource use data in inpatient and outpatient care during 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF) scores, were obtained from the Northern Stockholm psychiatric clinic with a catchment area including 47% of the adult inhabitants in Stockholm. This dataset was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of bipolar disorder. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual cost per patient was 28,011 in 2008 (n = 1,846). Indirect costs due to sick leave and early retirement represented 75%, inpatient costs 13%, outpatient costs 8%, pharmaceuticals 2% and community care another 2% of the total cost. Total costs were considerably higher during mood episodes (six times higher than in remission), for hospitalised patients (55,500 vs. 22,200) and for patients with low GAF scores. CONCLUSIONS: The high cost of bipolar disorder is driven primarily by indirect costs. Costs were strongly associated with mood episodes, hospitalisations and low GAF scores. This suggests that treatment that reduces the risk for relapses and hospitalizations and improve functioning may decrease both the societal cost of bipolar disorder and patient suffering.

The societal cost of schizophrenia in Sweden.

BACKGROUND: Schizophrenia is a disabling psychiatric disorder that has severe consequences for patients and their families. Moreover, the expensive treatment of schizophrenia imposes a burden on health care providers and the wider society. Existing cost estimates for Sweden, however, are based on relatively small patient populations and need to be confirmed in a large register-based study. AIMS OF THE STUDY: To investigate the health care resource utilization and cost-of-illness in patients with schizophrenia in Sweden and to relate the costs to hospitalizations and global assessment of functioning (GAF). METHODS: Hospital-based registry data were combined with national registry data from a large patient population to get reliable estimates of the costs of schizophrenia in Sweden. Schizophrenia was defined by ICD-10 codes F20; F21; F23.1,2,8,9; F25.1,8,9. Registry data on socio-demographics and disease-related healthcare resource use in outpatient and inpatient care were obtained from Northern Stockholm Psychiatry. Data on pharmaceuticals were obtained from the National Board of Health and Welfare, and data on sick leave and early retirement were obtained from the Swedish Social Insurance Agency. Costs for community mental health care were not available at the individual level, but were estimated based on previous studies and aggregate cost data from Stockholm. Resource use data from the registries were combined with unit costs from publicly available sources. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual psychiatric cost per patient with schizophrenia in 2008 was EUR 42700 (95% CI: EUR 41500-44000), based on a sample of 2161 patients. To this should be added costs for community mental health care of EUR 12400 per patient, giving a total cost of EUR 55100 per patient. The two largest cost items in the total costs were indirect costs due to lost productivity (60%) and community mental health care (22% of the total cost). Patients who were hospitalized in 2008 had greater psychiatric costs than those who were not, EUR 71700 vs. EUR 37700 (p<0.0001). Psychiatric costs were significantly and negatively correlated with GAF (p<0.001). DISCUSSION: The major strengths of the study are the relatively large sample, and the linkage of patient-level clinical data on inpatient and outpatient care with national registry data on prescription pharmaceuticals, and days on social insurance. A limitation was that costs for informal care and primary care were not included in the data, but previous studies suggest that these costs items are small compared to other costs for schizophrenia. IMPLICATIONS FOR HEALTH POLICIES AND FUTURE RESEARCH: Costs were strongly related to hospitalization and GAF, suggesting that attempts to improve global functioning and avoid hospitalizations by means of effective treatment and rehabilitation might not only decrease suffering for patients and relatives, but also reduce the societal cost of schizophrenia. A detailed knowledge of the societal costs can also be helpful in evaluating the cost-effectiveness of new treatment strategies to improve the care for patients with schizophrenia.

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.

Cost of disorders of the brain in Europe 2010.

BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people. AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country. METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010. RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US. DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges. RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials.

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

Economic evaluation of irbesartan in combination with hydrochlorothiazide in the treatment of hypertension in Greece.

OBJECTIVES: Hypertension is a major risk factor for cardiovascular disease and a leading cause of morbidity and mortality. This study evaluates irbesartan in relation to commonly used alternative hypertension therapies losartan and valsartan given in combination with hydrochlorothiazide (HCTZ) in the general hypertensive population in Greece. METHODS: A Markov model with eight states of health was constructed: hypertension, myocardial infarction (MI), post-MI, angina, stroke, poststroke, heart failure, and death. The model has an annual cycle and estimates mean quality-adjusted survival and treatment cost, which reflect the hypertension treatment and managing cardiovascular events. Risk functions were used to conduct extrapolations. Data on treatment effectiveness, quality of life (QOL) and epidemiology were obtained from published clinical trials and studies. The database of the main Greek National Social Insurance Institute (IKA) was analyzed to estimate the cost of events. The analysis was done from a payer perspective. All outcomes were discounted, and prices correspond to 2008. RESULTS: The estimated patient cost per annum was stable angina euro 2,252, unstable angina euro 2,572, myocardial infarction euro 2,473, post-MI euro 1,677, stroke euro 12,233, poststroke euro 1,240, heart failure euro 2,655, coronary angiography euro 1,544, percutaneous transluminal coronary angioplasty euro 6,511, and coronary artery bypass graft surgery euro 11,514. For the baseline group (age 57 years, systolic blood pressure 147 mmHg, cholesterol 6.00 mmol/L, body mass index 29) of men with mild to moderate hypertension, for irbesartan, the total treatment cost was euro 15,146, for losartan euro 15,696 and for valsartan euro 15,613; the quality-adjusted life years (QALYs) were irbesartan 12.67, losartan 12.63 and valsartan 12.64. For the baseline group of women with mild to moderate hypertension, the total treatment cost was euro 12,945 for irbesartan, euro 13,424 for losartan and euro 13,379 for valsartan; QALYs were 14.29 for irbesartan, 14.27 for losartan and 14.27 for valsartan. For men with severe hypertension, for irbesartan and losartan, the total treatment cost was euro 18,679 and euro 21,488 and QALYs 12.47 and 12.37, respectively. For women, the total treatment cost was euro 16,202 and euro 19,099 and QALYs 14.16 and 14.09, respectively. Similar results were obtained in relation to other treatment groups in various sensitivity analysis scenarios. CONCLUSIONS: Based on efficacy data from clinical trials and lower attainment costs in various hypertensive patient populations, irbesartan in combination with HCTZ compares favorably with losartan and valsartan in combination with HCTZ in the Greek setting.

Treatment options for bipolar depression: a systematic review of randomized, controlled trials.

This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.

Estimating the cost of epilepsy in Europe: a review with economic modeling.

PURPOSE: Based on available epidemiologic, health economic, and international population statistics literature, the cost of epilepsy in Europe was estimated. METHODS: Europe was defined as the 25 European Union member countries, Iceland, Norway, and Switzerland. Guidelines for epidemiological studies on epilepsy were used for a case definition. A bottom-up prevalence-based cost-of-illness approach, the societal perspective for including the cost items, and the human capital approach as valuation principle for indirect costs were used. The cost estimates were based on selected studies with common methodology and valuation principles. RESULTS: The estimated prevalence of epilepsy in Europe in 2004 was 4.3-7.8 per 1,000. The estimated total cost of the disease in Europe was euro15.5 billion in 2004, indirect cost being the single most dominant cost category (euro8.6 billion). Direct health care costs were euro2.8 billion, outpatient care comprising the largest part (euro1.3 billion). Direct nonmedical cost was euro4.2 billion. That of antiepileptic drugs was euro400 million. The total cost per case was euro2,000-11,500 and the estimated cost per European inhabitant was euro33. CONCLUSIONS: Epilepsy is a relevant socioeconomic burden at individual, family, health services, and societal level in Europe. The greater proportion of such burden is outside the formal health care sector, antiepileptic drugs representing a smaller proportion. Lack of economic data from several European countries and other methodological limitations make this report an initial estimate of the cost of epilepsy in Europe. Prospective incidence cost-of-illness studies from well-defined populations and common methodology are encouraged.

Health-related quality of life measured with EQ-5D in patients treated for depression in primary care.

OBJECTIVE: The objective of the present study was to assess the impact of depression on patients' health-related quality of life (HRQL) with the EQ-5D instrument over 6 months while on antidepressant treatment. METHODS: A total of 447 patients were recruited at 56 primary care centers to this naturalistic longitudinal observational study. Patients older than 18 years with depressive symptoms, and who initiated an antidepressant therapy because of depression were included in the study. Data on patients' sociodemographics, daily activity, and quality of life (EQ-5D) were collected using questionnaires completed during outpatient general practitioner visits for a follow-up period of 6 months. RESULTS: The mean EQ-5D utility score at baseline was 0.47 (0.44-0.49). Milder cases of depression reported a health utility of 0.60, whereas moderately and severely depressed patients reported utility values of 0.46 and 0.27, respectively (P < 0.01). At end of follow up the average utility was 0.69 (0.67-0.72), corresponding to an increase of 0.23 over 6 months (P < 0.01). Regression analyses showed that, all else equal, patients who were on sick leave were associated with 10% lower utility. CONCLUSIONS: Depression has a substantial impact on HRQL. Our results indicate that treatments for depression are associated with significant improvement in EQ-5D index score over a course of 6 months. Self-reported patient valuations are important outcomes for cost-utility analysis of new treatments for depression and the present study provides important evidence for future economic evaluations.

Health utilities in mild cognitive impairment and dementia: a population study in Sweden.

OBJECTIVE: To collect new primary data on community-based health utilities (time trade-off values) in different stages of mild cognitive impairment and dementia from a general population sample. METHODS: A cross-sectional study including 1,800 randomly selected members of the Swedish public aged 45-84 was performed through a postal survey; 42% response rate. The Clinical Dementia Rating scale was used for describing progressive stages of dementia in vignettes that were used in combination with time trade-off questions for valuing the perceived quality of life in these stages. RESULTS: The time-trade off values varied considerably across the progressive disease stages. The mean score was 0.82 for mild cognitive impairment, 0.62 for mild dementia, 0.40 for moderate dementia, and 0.25 for severe dementia. In multiple regression analyses, the scores were relatively insensitive to demographic factors like age, gender and self-assessed health. CONCLUSIONS: The results showed that the average time trade-off values declined sharply from mild cognitive impairment to progressing stages of dementia. Since there are many methodological challenges involved in measuring health state utilities in mild cognitive impairment and dementia, more research that evaluates different methods would be welcome.

Model to assess the cost-effectiveness of new treatments for depression.

OBJECTIVES: The objective of this study was to develop a model to assess the cost-effectiveness of a new treatment for patients with depression. METHODS: A Markov simulation model was constructed to evaluate standard care for depression as performed in clinical practice compared with a new treatment for depression. Costs and effects were estimated for time horizons of 6 months to 5 years. A naturalistic longitudinal observational study provided data on costs, quality of life, and transition probabilities. Data on long-term consequences of depression and mortality risks were collected from the literature. Cost-effectiveness was quantified as quality-adjusted life-years (QALYs) gained from the new treatment compared with standard care, and the societal perspective was taken. Probabilistic analyses were conducted to present the uncertainty in the results, and sensitivity analyses were conducted on key parameters used in the model. RESULTS: Compared with standard care, the new hypothetical therapy was predicted to substantially decrease costs and was also associated with gains in QALYs. With an improved treatment effect of 50 percent on achieving full remission, the net cost savings were 20,000 Swedish kronor over a 5-year follow-up time, given equal costs of treatments. Patients gained .073 QALYs over 5 years. The results are sensitive to changes in assigned treatment effects. CONCLUSIONS: The present study provides a new model for assessing the cost-effectiveness of treatments for depression by incorporating full remission as the treatment goal and QALYs as the primary outcome measure. Moreover, we show the usefulness of naturalistic real-life data on costs and quality of life and transition probabilities when modeling the disease over time.

Cost-effectiveness of the Taxus paclitaxel-eluting stent in the Swedish healthcare system.

OBJECTIVE: To analyse the cost-effectiveness of Taxus compared to a bare-metal stent in patients with coronary artery disease in the Swedish healthcare setting. DESIGN: A decision-analytic model combining clinical data on revascularization rates with Swedish unit costs for medical resources and utility data from the literature. RESULTS: For patients of moderate risk, the average cost per patient at 12 months is 72,200 SEK for Taxus and 66,900 SEK for a bare-metal stent, while the average cost for high risk patients is nearly equivalent (73,000 vs. 71,700 SEK). The cost per revascularization avoided is generally favourable, while the incremental cost per QALY gained varies depending on the assumptions made; from 2,351,000 SEK for patients of moderate risk at 12-months to cost saving at 24 months for high risk patients. Budget impact scenarios at 12 months are cost-neutral. CONCLUSION: The Taxus stent is cost-effective in high risk patients, particularly at 24 months. Although it may be less cost-effective for the general population, there is still a substantial offset of initial procedure costs through lower rate of repeat revascularizations.