sFlt-1/PlGF Ratio as a Predictive Marker in Women with Suspected Preeclampsia: An Economic Evaluation from a Swiss Perspective.

In Switzerland, 2.3% of pregnant women develop preeclampsia. Quantification of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio has shown a diagnostic value in the second and third trimesters of pregnancy, in particular in ruling out preeclampsia within one week. We estimated the economic impact of implementing sFlt-1/PlGF ratio evaluation, in addition to the standard of care (SOC), for women with suspected preeclampsia from a Swiss healthcare system's perspective. A decision tree model was developed to estimate direct medical costs of diagnosis and management of a simulated cohort of Swiss pregnant women with suspected preeclampsia (median week of gestation: 32) until delivery. The model compared SOC vs. SOC plus sFlt-1/PlGF ratio, using clinical inputs from a large multicenter study (PROGNOSIS). Resource use data and unit costs were obtained from hospital records and public sources. The assumed cost for sFlt-1/PlGF evaluation was €141. Input parameters were validated by clinical experts in Switzerland. The model utilized a simulated cohort of 6084 pregnant women with suspected preeclampsia (representing 7% of all births in Switzerland in 2015, n = 86,919). In a SOC scenario, 36% of women were hospitalized, of whom 27% developed preeclampsia and remained hospitalized until birth. In a sFlt-1/PlGF test scenario, 76% of women had a sFlt-1/PlGF ratio of ≤38 (2% hospitalized), 11% had a sFlt-1/PlGF ratio of >38-<85 (55% hospitalized), and 13% had a sFlt-1/PlGF ratio of ≥85 (65% hospitalized). Total average costs/pregnant woman (including birth) were €10,925 vs. €10,579 (sFlt-1/PlGF), and total costs were €66,469,362 vs. €64,363,060 (sFlt-1/PlGF). Implementation of sFlt-1/PlGF evaluation would potentially achieve annual savings of €2,105,064 (€346/patient), mainly due to reduction in unnecessary hospitalization. sFlt-1/PlGF evaluation appears economically promising in predicting short-term absence of preeclampsia in Swiss practice. Improved diagnostic accuracy and reduction in unnecessary hospitalization could lead to significant cost savings in the Swiss healthcare system.

Economic burden of symptomatic iron deficiency - a survey among Swiss women.

BACKGROUND: Symptomatic iron deficiency (ID) is a disorder affecting 10-20% of menstruating women. ID is diagnosed by measuring serum ferritin, a protein helping to store iron in the body. A deeper understanding of the association between ID and its societal and economic burden is relevant for patients, physicians, health care decision makers. METHODS: An online household survey was carried out among Swiss women aged 18-50 years suffering from debilitating symptoms due to ID. The data was population-weighted for age and region. The costs of misdiagnosis and the ID-related economic burden (i.e. days of sick leave) from productivity losses on the labor market were determined and extrapolated to the Swiss population. Furthermore, the patient burden was assessed based on quality of life daily measurements. RESULTS: The total sample included 1010 women who received an ID diagnosis with a blood test in the last 2 years (mean age: 33.5 years). Most named symptoms were "being tired or exhausted" (96.4%) and reduced physical energy level (41.0%). In total, 354 (35.0% of the total sample) patients received an initial diagnosis other than ID. Of those, 46.8% were treated prior to the ID diagnosis with a pharmacological medical therapy or psychotherapy. Extrapolating these numbers to the Swiss female population aged 18-50 years, the direct medical costs would be CHF 78 million (assuming an annual ID incidence of ID diagnosis of 9.5%). On average, 28.5% of participants in the work-force had to take sick leave due to ID symptoms within a period of 2 years (mean: 5.2 days, i.e. 2.6 days/year). The estimated annual indirect costs in Switzerland would be CHF 33 million (human capital approach) or CHF 26 million (friction cost method), respectively. Being exhausted and impaired concentration appear to be the most important factors negatively impacting daily living and hence quality of life. CONCLUSION: The societal and economic burden among women due to debilitating symptoms of ID in Switzerland is substantial. Timely, correct diagnosis and treatment of ID may contribute to reducing this burden. Further studies are needed in this area to validate our results.

Cost Effectiveness of Sucroferric Oxyhydroxide Compared with Sevelamer Carbonate in the Treatment of Hyperphosphataemia in Patients Receiving Dialysis, from the Perspective of the National Health Service in Scotland.

BACKGROUND: Hyperphosphataemia is common and harmful in patients receiving dialysis. Treatment options include noncalcium-based phosphate binders such as sevelamer carbonate (SC) and sucroferric oxyhydroxide (PA21). OBJECTIVE: The aim of this study was to determine the health economic impact of PA21-based strategies compared with SC-based strategies, from the perspective of the Scottish National Health Service (NHS). METHODS: A Markov model was constructed based on data from a randomised clinical trial comparing PA21 and SC. Model input parameters were derived from published literature, national statistics and unpublished sources. Costs (price year 2012) and effects were discounted at 3.5 %. Analysis with a lifelong time horizon yielded the incremental cost-effectiveness ratio (ICER), expressed as cost or savings per quality-adjusted life-year (QALY) gained or forgone. Deterministic and probabilistic sensitivity analysis was performed to explore uncertainties around assumptions and model input parameters. RESULTS: In the base-case analysis, phosphorus reductions for PA21 and SC were 1.93 and 1.95 mg/dL. Average undiscounted survival was estimated to be 7.61 years per patient in both strategies. PA21 patients accrued less QALYs (2.826) than SC patients (2.835), partially due to differential occurrence of side effects. Total costs were £ 13,119 and £ 14,728 for PA21 and SC, respectively (difference per patient of £ 1609). By using PA21 versus SC, one would save £ 174,999 (or £ 123,463 when including dialysis and transplantation costs) for one QALY forgone. A scenario modelling the nonsignificant reduction in mortality (relative risk 0.714) observed in the trial yielded an ICER for PA21 of £ 22,621 per QALY gained. In probabilistic sensitivity analysis of the base-case, PA21 was dominant in 11 %, and at least cost-effective in 53 %, of iterations, using a threshold of £ 20,000 per QALY gained. CONCLUSIONS: The use of PA21 versus SC in hyperphosphataemic patients being intolerant of calcium-based phosphate binders may be cost saving and yields only very limited disadvantages in terms of quality-adjusted survival. PA21 appears to be cost-effective from the perspective of the Scottish NHS.

Cost-effectiveness analysis of prognostic gene expression signature-based stratification of early breast cancer patients.

BACKGROUND: The individual risk of recurrence in hormone receptor-positive primary breast cancer patients determines whether adjuvant endocrine therapy should be combined with chemotherapy. Clinicopathological parameters and molecular tests such as EndoPredict(®) (EPclin) can support decision making in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative cancer. OBJECTIVE: Using a life-long Markov state transition model, we determined the health economic impact and incremental cost effectiveness of EPclin-based risk stratification in combination with clinical guidelines [German-S3, National Comprehensive Cancer Center Network (NCCN), and St. Gallen] to decide on chemotherapy use. METHODS: Information on overall and metastasis-free survival came from Austrian Breast & Colorectal Cancer Study Group clinical trials 6/8 (n = 1,619) and published literature. Effectiveness was assessed as quality-adjusted life-years (QALYs). Costs (2010) were assessed from a German third-party payer perspective. RESULTS: Lifetime costs per patient ranged from 28,268 (St.Gallen and EPclin) to 33,756 (NCCN). Due to an imperfect prognostic value and differences in chemotherapy use, strategies achieved between 13.165 QALYs (NCCN) and 13.173 QALYs (EPclin alone) per patient. Using German-S3 as reference, three strategies showed dominant results (St. Gallen and EPclin, German-S3 and EPclin, EPclin alone). Compared to German-S3, the addition of EPclin saved 3,388 and gained 0.002 QALYs per patient. Combining guidelines with EPclin remained preferable in sensitivity analysis. CONCLUSION: Our study suggests that molecular markers can be sensibly combined with clinical guidelines to determine the risk profile of adjuvant breast cancer patients. Compared with the current German best practice (German-S3), combinations of EPclin with the St. Gallen, German-S3 or NCCN guideline and EPclin alone were dominant from the perspective of the German healthcare system.

The use of the EVITA algorithm for clinical assessment of novel agents used in prostate cancer, metastatic melanoma, and systemic lupus erythematosus.

PURPOSE: Existing health technology assessment methods can be time-consuming and complicated to use in practice. EValuation of pharmaceutical Innovations with regard to Therapeutic Advantage (EVITA) is a recently developed drug assessment strategy that provides a detailed and clinically relevant evaluation of new agents compared to standard therapies. We therefore sought to use EVITA to evaluate eight novel agents recently introduced to clinical practice or in late-stage trials for the treatment of prostate cancer, metastatic melanoma, or systemic lupus erythematosus (SLE). METHODS: Eight agents (abiraterone, enzalutamide, sipuleucel-T, Prostvac, radium 223, ipilimumab, vemurafenib, and belimumab) were selected for study using the EVITA algorithm. A comprehensive literature search was performed to find clinical trial data, which were then classified using the EVITA protocol. EVITA was also compared to results from health technology assessments (HTAs) or reimbursement decisions. RESULTS: The EVITA scores for the eight drugs ranged from 5.5 to 9: all the selected agents are therefore classed as 'recommended' and are likely to produce a therapeutic advantage. In particular, vemurafenib is likely to be highly beneficial to patients with metastatic melanoma and radium 223 to patients with metastatic prostate cancer affecting the bone. The EVITA results were generally concordant with HTAs. CONCLUSIONS: All the agents show favourable EVITA scores and are therefore recommended for clinical practice. EVITA is an easy-to-use tool that provides clinical context to the assessment of newly introduced agents and can be easily used by non-specialists.

Population access to new vaccines in European countries.

Time from registration to population access to new vaccines can take considerable time in European countries. Reasons might be found in the regulatory framework, decision-making processes or the assessment of vaccines by evaluating bodies. The aim of this study was to determine whether some decision-making processes can explain between-country differences in the time to population access to new vaccination programs. Information gathered from a survey among European National Vaccine Industry Groups was combined with information from official health authorities, vaccine manufacturers and literature published. Firstly, a retrospective survey was conducted to measure access time to new vaccines against three diseases in 17 European countries. Secondly, qualitative information on the country-specific decision-making frameworks for the introduction of new "vaccination programs" was identified in a cross-sectional survey. Spearman's rank correlation coefficients (ρ) were used for data analysis. The median access time to new vaccines was 6.4 years (95% confidence interval: 5.7-7.1 years) post marketing authorization. National assessments underlying immunization policy decisions (recommendation phase) absorbed most of the access time. Correlation analysis suggested that processes with established timelines and clarity in regard to vaccine evaluation criteria used could ameliorate the effectiveness of the decision-making process. In order to reduce the time to access for new, beneficial vaccines, the underlying vaccination recommendation, implementation and funding process needs to be understood and optimized, where necessary.

Health economic assessment of ferric carboxymaltose in patients with iron deficiency and chronic heart failure based on the FAIR-HF trial: an analysis for the UK.

AIMS: The purpose of this study was to evaluate the cost-effectiveness of iron repletion using intravenous (i.v.) ferric carboxymaltose (FCM) in chronic heart failure (CHF) patients with iron deficiency with or without anaemia. Cost-effectiveness was studied from the perspective of the National Health Service in the UK. METHODS AND RESULTS: A model-based cost-effectiveness analysis was used to compare iron repletion with FCM with no iron treatment. Using data from the FAIR-HF trial and publicly available sources and publications, per patient costs and clinical effectiveness of FCM were estimated compared with placebo. Cost assessment was based on study drug and administration costs, cost of CHF treatment, and hospital length of stay. The incremental cost-effectiveness ratio (ICER) of FCM use was expressed as cost per quality-adjusted life year (QALY) gained, and sensitivity analyses were performed on the base case. The time horizon of the analysis was 24 weeks. Mean QALYs were higher in the FCM arm (difference 0.037 QALYs; bootstrap-based 95% confidence interval 0.017-0.060). The ICER of FCM compared with placebo was €4414 per QALY gained for the FAIR-HF dosing regimen. Sensitivity analyses confirmed the base case result to be robust. CONCLUSION: From the UK payers' perspective, managing iron deficiency in CHF patients using i.v. FCM was cost-effective in this analysis. The base case ICER was clearly below the threshold of €22 200-€33 300/QALY gained (£20 000-£30 000) typically used by the UK National Institute for Health and Clinical Excellence and proved to be robust in sensitivity analysis. Improved symptoms and better quality of life contributed to this result.

KRAS and BRAF mutation analysis in metastatic colorectal cancer: a cost-effectiveness analysis from a Swiss perspective.

PURPOSE: Monoclonal antibodies against the epidermal growth factor receptor (EGFR), such as cetuximab, have led to significant clinical benefits for metastatic colorectal cancer (mCRC) patients but have also increased treatment costs considerably. Recent evidence associates KRAS and BRAF mutations with resistance to EGFR antibodies. We assessed the cost-effectiveness of predictive testing for KRAS and BRAF mutations, prior to cetuximab treatment of chemorefractory mCRC patients. EXPERIMENTAL DESIGN: A life-long Markov simulation model was used to estimate direct medical costs (€) and clinical effectiveness [quality-adjusted life-years (QALY)] of the following strategies: KRAS testing, KRAS testing with subsequent BRAF testing of KRAS wild-types (KRAS/BRAF), cetuximab treatment without testing. Comparison was against no cetuximab treatment (reference strategy). In the testing strategies, cetuximab treatment was initiated if no mutations were detected. Best supportive care was given to all patients. Survival times/utilities were derived from published randomized clinical trials. Costs were assessed from the perspective of the Swiss health system. RESULTS: Average remaining lifetime costs ranged from €3,983 (no cetuximab) to €38,662 (no testing). Cetuximab treatment guided by KRAS/BRAF achieved gains of 0.491 QALYs compared with the reference strategy. The KRAS testing strategy achieved an additional gain of 0.002 QALYs compared with KRAS/BRAF. KRAS/BRAF testing was the most cost-effective approach when compared with the reference strategy (incremental cost-effectiveness ratio: €62,653/QALY). CONCLUSION: New predictive tests for KRAS and BRAF status are currently being introduced in pathology. Despite substantial costs of predictive testing, it is economically favorable to identify patients with KRAS and BRAF wild-type status.

Cost-effectiveness analysis of malaria chemoprophylaxis for travellers to West-Africa.

BACKGROUND: The importation of malaria to non-endemic countries remains a major cause of travel-related morbidity and a leading cause of travel-related hospitalizations. Currently they are three priority medications for malaria prophylaxis to West Africa: mefloquine, atovaquone/proguanil and doxycycline. We investigate the cost effectiveness of a partial reimbursement of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers to high risk areas of malaria transmission compared with the current situation of no reimbursement. METHODS: This study is a cost-effectiveness analysis based on malaria cases imported from West Africa to Switzerland from the perspective of the Swiss health system. We used a decision tree model and made a literature research on the components of travel related malaria. The main outcome measure was the cost effectiveness of malaria chemoprophylaxis reimbursement based on malaria and deaths averted. RESULTS: Using a program where travellers would be reimbursed for 80% of the cost of the cheapest malaria chemoprophylaxis is dominant (i.e. cost saving and more effective than the current situation) using the assumption that currently 68.7% of travellers to West Africa use malaria chemoprophylaxis. If the current usage of malaria chemoprophylaxis would be higher, 82.4%, the incremental cost per malaria case averted is € 2'302. The incremental cost of malaria death averted is € 191'833.The most important factors influencing the model were: the proportion of travellers using malaria chemoprophylaxis, the probability of contracting malaria without malaria chemoprophylaxis, the cost of the mefloquine regimen, the decrease in the number of travellers without malaria chemoprophylaxis in the reimbursement strategy. CONCLUSIONS: This study suggests that a reimbursement of 80% of the cost of the cheapest effective malaria chemoprophylaxis (mefloquine) for travellers from Switzerland to West Africa is highly effective in terms of malaria cases averted and is cost effective to the Swiss health system. These data are relevant to discussions about the cost effectiveness of malaria chemoprophylaxis reimbursement for vulnerable groups such as those visiting friends and relatives who have the highest risk of malaria, who are least likely to use chemoprophylaxis.

Cost effectiveness of cytotoxic and targeted therapy for metastatic breast cancer: a critical and systematic review.

Breast cancer is the leading cancer type diagnosed among women in Western countries. Despite great advances in cancer therapies, many of these patients develop non-curable metastases. The objective of cancer treatment in the metastatic setting is mainly to control symptoms and to prolong survival. The selection of the optimal chemotherapeutic regimen is affected by performance status, tumour biology, site and extent of the disease and the exposure to prior therapies. Recent developments in new kinds of cancer drugs have contributed not only to immense progress in clinical outcomes but also to dramatically increased treatment-related health costs. Cost-effectiveness analysis is a type of economic evaluation that compares costs and health outcomes of alternative intervention strategies in a systematic way. In this review, a systematic literature search was performed and the evidence on the cost effectiveness of conventional chemotherapy and targeted therapy for metastatic breast cancer was explored. Cost-effectiveness/-utility analysis of treatment regimens for metastatic breast cancer were identified using literature and reference searches (MEDLINE). Published reports on conventional and targeted cancer therapies were scrutinized and incremental cost-effectiveness ratios (ICERs) were abstracted. Furthermore, the quality of reporting, as well as methodological and modeling issues, were extensively discussed. From full-text article reviews, six cost-effectiveness analyses on conventional therapies and seven studies on targeted therapies were included. Eight analyses were conducted in European countries, three in the US and two in Canada. The economic models were primarily (69%) based on clinical trial data. Results from sensitivity analyses and study perspectives were reported by all studies. Discount rates were mentioned in five articles (39%). The methods of reporting costs and effects varied considerably, as did trial design across conventional chemotherapies, which made it difficult to compare those analyses. The pharmacoeconomic studies came to different conclusions. The actual clinical evidence does not suggest one conventional chemotherapy regimen as superior. Studies on cytotoxic agents showed mainly favourable cost-effectiveness ratios. Targeted therapies indicated both favourable and non-favourable ratios. Currently, trastuzumab is the only antibody-based targeted therapy that is established in the clinic for the metastatic setting.

Human epidermal growth factor receptor 2 expression in early breast cancer patients: a Swiss cost-effectiveness analysis of different predictive assay strategies.

Trastuzumab has conferred significant clinical benefits in HER-2-positive breast carcinomas. HER-2 status is determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridisation (FISH), but appropriate assessment of HER2 status remains subject to considerable debate. Data on the health economic impact of HER-2 test strategies are limited. A life-long Markov state transition model was used to assess costs and effectiveness of HER-2 assay strategies (based on IHC, FISH, both combined or FISH confirmation of IHC2+) for a hypothetical cohort of early breast cancer patients from the perspective of the Swiss health system. We compared clinically relevant strategies of predictive testing and subsequent trastuzumab treatment of HER-2-positive patients only. FISH testing was the most cost-effective strategy with an incremental cost-effectiveness ratio of €12,245 per additional quality-adjusted life-year (QALY) gained, compared to no trastuzumab treatment. The next best strategy was parallel IHC and FISH, with costs of €400,154/QALY gained compared to FISH alone. FISH as primary HER-2 testing modality remained the preferred option in deterministic and probabilistic sensitivity analysis. Predictive testing to identify adjuvant breast cancer patients who benefit from trastuzumab treatment is a clinical and economic necessity. Our model identifies FISH as the most cost-effective approach.

Developments in influenza vaccination coverage in England, Scotland and Wales covering five consecutive seasons from 2001 to 2006.

This study aims at assessing trends in influenza vaccination coverage from 2001 to 2006 in Great Britain, at understanding drivers and barriers to vaccination and at identifying vaccination intentions for influenza season 2006/2007. In seasons 2001/2002 to 2005/2006, telephone-based household surveys representative of the population from age 16 were conducted, with about 2000 interviews per season (10,095 in total). Overall influenza vaccination coverage rate in Great Britain reached 25.9% in season 2005/2006. A sub-analysis showed that the highest coverage was reported in Wales reaching 33.3%. In the elderly recommended vaccination (from age 65), the coverage reached 79% in 2005/2006. Advice from the family doctor and the perception that influenza is a serious illness were the most frequent reasons for getting vaccinated. The most frequent reasons for not getting vaccinated, in persons never vaccinated before, were that they had not considered immunisation or had not received a recommendation from their family doctor. Those vaccinated in the past but not in the current season said they had not thought about vaccination/forgot. A gap continues to exist between those with intention to get vaccinated and those actually vaccinated, indicating a potential to increase vaccination coverage rate in the future. Our study shows that stable vaccination coverage rates were observed from 2002 to 2006 in Great Britain. The coverage had increased in Wales and in Scotland. The coverage among the elderly above 65 years was the highest in Europe. Although Great Britain complies with national and international goals of vaccination coverage rates effort is needed to ensure high vaccination coverage rates at the same level in the future.