Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role towards personalised medicine remains uncertain. Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) is an European collaborative research project with the primary objective to assess the value of established and emerging biomarkers for cardiovascular risk prediction. BiomarCaRE integrates clinical and epidemiological biomarker research and commercial enterprises throughout Europe to combine innovation in biomarker discovery for cardiovascular disease prediction with consecutive validation of biomarker effectiveness in large, well-defined primary and secondary prevention cohorts including over 300,000 participants from 13 European countries. Results from this study will contribute to improved cardiovascular risk prediction across different European populations. The present publication describes the rationale and design of the BiomarCaRE project.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-014-9952-x) contains supplementary material, which is available to authorized users.

Objectives Progression-free survival (PFS) has not been validated as a surrogate endpoint for overall survival (OS) for anthracycline (A) and taxane-based (T) chemotherapy in advanced breast cancer (ABC). Using trial-level, meta-analytic approaches, we evaluated PFS as a surrogate endpoint. Methods A literature review identified randomized, controlled A and T trials for ABC. Progression-based endpoints were classified by prospective definitions. Treatment effects were derived as hazard ratios for PFS (HRPFS) and OS (HROS). Kappa statistic assessed overall agreement. A fixed-effects regression model was used to predict HROS from observed HRPFS. Cross-validation was performed. Sensitivity and subgroup analyses were performed for PFS definition, year of last patient recruitment, line of treatment, and constant rate assumption. Results Sixteen A and fifteen T trials met inclusion criteria, producing seventeen A (n = 4,323) and seventeen T (n = 5,893) trial-arm pairs. Agreement (kappa statistic) between the direction of HROS and HRPFS was 0.71 for A (p = .0029) and 0.75 for T (p = .0028). While HRPFS was a statistically significant predictor of HROS for both A (p = .0019) and T (p = .012), the explained variances were 0.49 (A) and 0.35 (T). In cross-validation, 97 percent of the 95 percent prediction intervals crossed the equivalence line, and the direction of predicted HROS agreed with observed HROS in 82 percent (A) and 76 percent (T). Results were robust in sensitivity and subgroup analyses. Conclusions This meta-analysis suggests that the trial-level treatment effect on PFS is significantly associated with the trial-level treatment effect on OS. However, prediction of OS based on PFS is surrounded with uncertainty.

Background and aims: While management programmes (MPs) for chronic heart failure (CHF) are clinically effective, their cost-effectiveness remains uncertain. Thus, this study sought to determine the cost-effectiveness of MPs. Methods and results:We developed a Markov model to estimate life expectancy, quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness of MPs as compared to standard care. Standard care was defined by the EuroHeart Failure Survey for Germany, MP efficacy was derived from our recent meta-analysis and cost estimates were based on the German healthcare system. For a population with a mean age 67 years (35% female) at onset of CHF, our model predicted an average quality-adjusted life expectancy of 2.64 years for standard care and 2.83 years for MP. MP yielded additional lifetime costs of €1700 resulting in an incremental cost-utility ratio (ICUR) of €8900 (95% CI: dominant to 177,100) per quality-adjusted life year (QALY) gained. Sensitivity analyses demonstrated that the ICUR was sensitive to age and sex. Conclusion: MPs increase life expectancy in patients with CHF by an average of 84 days and increase lifetime cost of care by approximately €1700. MPs improve outcomes in a cost-effective manner, although they are not cost-saving on a lifetime horizon.

HCV screening and early treatment have the potential to improve average life-expectancy, but should focus on populations with elevated HCV prevalence to be cost-effective. Further research on the long-term health-economic impact of HCV screening when combined with appropriate monitoring strategies in different European health care systems is needed.

We systematically reviewed the evidence for long-term effectiveness and cost-effectiveness of antiviral treatment in patients with chronic hepatitis C. We performed a systematic literature search on the long-term effectiveness and cost-effectiveness of AVT in hepatitis C (1990-March 2007), and included health technology assessment (HTA) reports, systematic reviews, long-term clinical trials, economic studies conducted alongside clinical trials and decision-analytic modelling studies. All costs were converted to 2005euro. Antiviral therapy with peginterferon plus ribavirin in treatment-naïve patients with chronic hepatitis C was the most effective (3.6-4.7 life years gained [LYG]) treatment and was reasonably cost-effective (cost-saving to 84 700euro/quality adjusted life years [QALY]) when compared to interferon plus ribavirin. Some results also suggest cost-effectiveness (below 8400euro/(QALY) of re-treatment in nonresponders/relapsers. Results for patients with persistently normal alanine aminotransferase (ALT) levels or with special co-morbidities (e.g. HIV) or risk profiles were rare. We conclude that antiviral therapy may prolong life, improve long-term health-related quality-of-life and be reasonably cost-effective in treatment-naïve patients with chronic hepatitis C as well as in former relapsers/nonresponders. Further research is needed in patients with specific co-morbidities or risk profiles.

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Chronic heart failure (CHF) is a critical public health issue with increasing effect on the healthcare budgets of developed countries. Various decision-analytic modelling approaches exist to estimate the cost effectiveness of health technologies for CHF. We sought to systematically identify these models and describe their structures. We performed a systematic literature review in MEDLINE/PreMEDLINE, EMBASE, EconLit and the Cost-Effectiveness Analysis Registry using a combination of search terms for CHF and decision-analytic models. The inclusion criterion required 'use of a mathematical model evaluating both costs and health consequences for CHF management strategies'. Studies that were only economic evaluations alongside a clinical trial or that were purely descriptive studies were excluded. We identified 34 modelling studies investigating different interventions including screening (n = 1), diagnostics (n = 1), pharmaceuticals (n = 15), devices (n = 13), disease management programmes (n = 3) and cardiac transplantation (n = 1) in CHF. The identified models primarily focused on middle-aged to elderly patients with stable but progressed heart failure with systolic left ventricular dysfunction. Modelling approaches varied substantially and included 27 Markov models, three discrete-event simulation models and four mathematical equation sets models; 19 studies reported QALYs. Three models were externally validated. In addition to a detailed description of study characteristics, the model structure and output, the manuscript also contains a synthesis and critical appraisal for each of the modelling approaches. Well designed decision models are available for the evaluation of different CHF health technologies. Most models depend on New York Heart Association (NYHA) classes or number of hospitalizations as proxy for disease severity and progression. As the diagnostics and biomarkers evolve, there is the hope for better intermediate endpoints for modelling disease progression as those that are currently in use all have limitations.

Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121,400 €/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131,100 €/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152,400 €/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy.