Budget impact of intravenous iron therapy with ferric carboxymaltose in patients with chronic heart failure and iron deficiency in Germany.

AIMS: Treatment of iron deficiency (ID) in patients with heart failure (HF) with intravenous iron substitution [ferric carboxymaltose (FCM)] has previously shown significant improvements in exercise capacity, New York Heart Association (NYHA) functional class, quality of life, and reduction of hospitalization. The aim of this study was to estimate the budget impact of FCM treatment for patients with HF and ID. METHODS AND RESULTS: Individual patient data from four double-blind randomized controlled trials were pooled for this analysis. Expected outcomes were modelled for a treatment period of 1 year, using multivariate statistical methods. Associated unit costs were derived from claims data. Budget impact was calculated from the perspective of the Statutory Health Insurance. Multiple deterministic sensitivity analyses were performed. The annual budget impact for therapy with FCM vs. no-iron therapy was €2 735 505 and €2 695 474 for 1000 patients, respectively, resulting in additional annual costs of €40.03 for each treated patient. Main costs drivers are the FCM treatment cost and cost of hospitalizations due to HF worsening. FCM therapy compared with no-iron therapy resulted in reduced cost per 1000 patients: for reduced hospitalization due to HF worsening (52 vs. 129 hospitalizations amounting to €230 591 vs. €597 078), for reduced other medication (€1 611 007 vs. €1 679 908), fewer outpatient visits (€332 523 vs. €378 019), and home visits (€29 627 vs. €40 469). Sensitivity analyses showed robustness of the results. CONCLUSIONS: Therapy with FCM has a minimal budget impact of €40 031 per 1000 patients per year. This budget impact translates into reduced and shorter hospitalizations and improved symptomatic status of the patients.

Benefit assessment in Germany: implications for price discounts.

BACKGROUND: The AMNOG regulation, introduced in 2011 in Germany, changed the game for new drugs. Now, the industry is required to submit a dossier to the GBA (the central decision body in the German sickness fund system) to show additional benefit. After granting the magnitude of the additional benefit by the GBA, the manufacturer is entitled to negotiate the reimbursement price with the GKV-SV (National Association of Statutory Health Insurance Funds). The reimbursement price is defined as a discount on the drug price at launch. As the price or discount negotiations between the manufacturers and the GKV-SV takes place behind closed doors, the factors influencing the results of the negotiation are not known. OBJECTIVES: The aim of this evaluation is to identify factors influencing the results of the AMNOG price negotiation process. METHODS: The analysis was based on a dataset containing detailed information on all assessments until the end of 2015. A descriptive analysis was followed by an econometric analysis of various potential factors (benefit rating, size of target population, deviating from appropriate comparative therapy and incorporation of HRQoL-data). RESULTS: Until December 2015, manufacturers and the GKV-SV finalized 96 negotiations in 193 therapeutic areas, based on assessment conducted by the GBA. The GBA has granted an additional benefit to 100/193 drug innovations. Negotiated discount was significantly higher for those drugs without additional benefit (p = 0.030) and non-orphan drugs (p = 0.015). Smaller population size, no deviation from recommended appropriate comparative therapy and the incorporation of HRQoL-data were associated with a lower discount on the price at launch. However, neither a uni- nor the multivariate linear regression showed enough power to predict the final discount. CONCLUSIONS: Although the AMNOG regulation implemented binding and strict rules for the benefit assessment itself, the outcome of the discount negotiations are still unpredictable. Obviously, negotiation tactics, the current political situation and soft factors seem to play a more influential role for the outcome of the negotiations than the five hard and known factors analyzed in this study. Further research is needed to evaluate additional factors.

Vaccination of children with a live-attenuated, intranasal influenza vaccine - analysis and evaluation through a Health Technology Assessment.

BACKGROUND: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the The German Standing Committee on Vaccination (STIKO) as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV) has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV) has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV) for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA) is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view. METHOD: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++), if they met the criteria of European Medicines Agency (EMA)-Guidance: Points to consider on applications with 1. meta-analyses; 2. one pivotal study. RESULTS: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction - RRR - of laboratory confirmed influenza infection approx. 80% and 50%, respectively). In children aged >7 to 17 years (= 18th year of their lives), LAIV is superior to a vaccination with TIV (RRR 32%). For this age group, no studies that compared LAIV with placebo were identified. It can be concluded that there is high evidence for superior efficacy of LAIV (compared to placebo or TIV) among children aged 6 months to ≤7 years. For children from >7 to 17 years, there is moderate evidence for superiority of LAIV for children with asthma, while direct evidence for children from the general population is lacking for this age group. Due to the efficacy of LAIV in children aged 6 months to ≤7 years (high evidence) and the efficacy of LAIV in children with asthma aged >7 to 17 years (moderate evidence), LAIV is also very likely to be efficacious among children in the general population aged >7 to 17 years (indirect evidence). In the included studies with children aged 2 to 17 years, LAIV was safe and well-tolerated; while in younger children LAIV may increase the risk of obstruction of the airways (e.g. wheezing). In the majority of the evaluated epidemiological studies, LAIV proved to be effective in the prevention of influenza among children aged 2-17 years under everyday conditions (effectiveness). The trend appears to indicate that LAIV is more effective than TIV, although this can only be based on limited evidence for methodological reasons (observational studies). In addition to a direct protective effect for vaccinated children themselves, indirect protective ("herd protection") effects were reported among non-vaccinated elderly population groups, even at relatively low vaccination coverage of children. With regard to safety, LAIV generally can be considered equivalent to TIV. This also applies to the use among children with mild chronically obstructive conditions, from whom LAIV therefore does not have to be withheld. In all included epidemiological studies, there was some risk of bias identified, e.g. due to residual confounding or other methodology-related sources of error. In the evaluated studies, both the vaccination of children with previous illnesses and the routine vaccination of (healthy) children frequently involve cost savings. This is especially the case if one includes indirect costs from a societal perspective. From a payer perspective, a routine vaccination of children is often regarded as a highly cost-effective intervention. However, not all of the studies arrive at consistent results. In isolated cases, relatively high levels of cost-effectiveness are reported that make it difficult to perform a conclusive assessment from an economic perspective. Based on the included studies, it is not possible to make a clear statement about the budget impact of using LAIV. None of the evaluated studies provides results for the context of the German healthcare setting. The efficacy of the vaccine, physicians' recommendations, and a potential reduction in influenza symptoms appear to play a role in the vaccination decision taken by parents/custodians on behalf of their children. Major barriers to the utilization of influenza vaccination services are a low level of perception and an underestimation of the disease risk, reservations concerning the safety and efficacy of the vaccine, and potential side effects of the vaccine. For some of the parents surveyed, the question as to whether the vaccine is administered as an injection or nasal spray might also be important. CONCLUSION: In children aged 2 to 17 years, the use of LAIV can lead to a reduction of the number of influenza cases and the associated burden of disease. In addition, indirect preventive effects may be expected, especially among elderly age groups. Currently there are no data available for the German healthcare setting. Long-term direct and indirect effectiveness and safety should be supported by surveillance programs with a broader use of LAIV. Since there is no general model available for the German healthcare setting, statements concerning the cost-effectiveness can be made only with precaution. Beside this there is a need to conduct health eco-nomic studies to show the impact of influenza vaccination for children in Germany. Such studies should be based on a dynamic transmission model. Only these models are able to include the indirect protective effects of vaccination correctly. With regard to ethical, social and legal aspects, physicians should discuss with parents the motivations for vaccinating their children and upcoming barriers in order to achieve broader vaccination coverage. The present HTA provides an extensive basis for further scientific approaches and pending decisions relating to health policy.

Pneumococcal vaccination rates in adults in Germany: an analysis of statutory health insurance data on more than 850,000 individuals.

BACKGROUND: The German Standing Committee on Vaccination Recommendations (Ständige Impfkommission, STIKO) recommends standard vaccination against pneumococcal infections for all persons aged 60 or older, and for all persons of any age with an increased health risk. It is not known how many persons in the target group in Germany have actually been vaccinated. METHOD: We used claims data of a German statutory health insurance (Deutsche BKK) to determine pneumococcal vaccination rates, stratified by age and risk, for the one-year period 1 July 2008 to 30 June 2009. The number of influenza vaccinations in the same period was analyzed for comparison. Because pneumococcal vaccination does not need to be performed annually, the calculated rates are an underestimate of the percentage of persons who have been vaccinated. A simulation model was used to correct for persons vaccinated at earlier times. The vaccination rates were estimated on the basis of various scenarios. RESULTS: Data were obtained on 867 683 persons aged 18 or older. According to an optimistic estimate, the percentage of pneumococcal vaccination in the overall population is 3.75% for persons aged 18-59 and 50.89% for persons aged 60 and above (influenza: 8.80% and 41.15%, respectively). In persons at elevated risk, the rate of vaccination in the presence of at least one risk factor is 12.66% / 54.67% (influenza: 15.66% / 39.96%). In persons with moderate risk, the vaccination rate is 16.02% / 56.75% (influenza: 18.54% / 40.61%); in persons whose elevated risk was high, it is 8.93% / 52.21% (influenza: 7.37%/37.78%). The limitations of this study are the short study period and the inability to define the population at risk unambiguously. CONCLUSION: The rate of pneumococcal vaccination in adults in Germany is too low; at best, it is comparable to that of influenza vaccination. These results should be validated by nationwide monitoring of the pneumococcal vaccination program. For example, questions about pneumococcal vaccination could be included in the GEDA study (German Health Update) that is conducted annually by the Robert Koch Institute.

Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany.

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix(®) or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

Potential cost-effectiveness and benefit-cost ratios of adult pneumococcal vaccination in Germany.

BACKGROUND: Invasive (IPD, defined as detection of pneumococci in sterile body fluids like meningitis or bacteremic pneumonia) and non-invasive Streptococcus pneumoniae infections (i.e. non-bacteremic pneumonia, otitis media) in adults are associated with substantial morbidity, mortality and costs. In Germany, Pneumococcal polysaccharide vaccination (PPV23) is recommended for all persons >60 years and for defined risk groups (age 5-59). The aim of this model was to estimate the potential cost-effectiveness and benefit-cost ratios of the adult vaccination program (18 years and older), considering the launch of the pneumococcal conjugate vaccine for adults (PCV13). METHODS: A cross-sectional steady state Markov model was developed to estimate the outcomes of PCV13, PPV23 vaccination schemes and 'no vaccination'. Conservative assumptions were made if no data were available for PCV13 and PPV23 respectively. The effectiveness of individual pneumococcal vaccination in adults was adjusted for expected indirect effects due to the vaccination in infants. Data on incidences, effectiveness and costs were derived from scientific literature and publicly available databases. All resources used are indicated. Benefit-cost ratios and cost-effectiveness were evaluated from the perspective of the German Statutory Health Insurance as well as from social perspective. RESULTS: Under the assumption that PCV13 has a comparable effectiveness to PCV7, a vaccination program with PCV13 revealed the potential to avoid a greater number of yearly cases and deaths in IPD and pneumonia in Germany compared to PPV23. For PCV13, the costs were shown to be overcompensated by monetary savings resulting from reduction in the use of health care services. These results would render the switch from PPV23 to PCV13 as a dominant strategy compared to PPV23 and 'no vaccination'. Given the correctness of the underlying assumptions every Euro spent on the PCV13 vaccination scheme yields savings of 2.09 € (social perspective: 2.16 €) compared to PPV23 and 1.27 € (social perspective: 1.32 €) compared to 'no vaccination', respectively. CONCLUSIONS: Results of the model indicate that the health economic benefit of immunizing adults with PCV13 can be expected to outperform the sole use of PPV23, if the effectiveness of PCV13 is comparable to the effectiveness of PCV7.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine: Germany, Greece, and The Netherlands.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) had profound public-health impacts and is considered cost-effective and potentially cost saving. Two new PCVs have been launched, a 10-valent vaccine (PCV10) and a 13-valent vaccine (PCV13). We examined public-health and economic impacts of PCV pediatric national immunization programs (NIPs) in Germany, Greece, and the Netherlands. METHODS: A decision-analytic model was developed to estimate the impact of PCV13, PCV7, and 10-valent pneumococcal conjugate vaccine (PCV10) on invasive pneumococcal disease (IPD), pneumonia (PNE), and acute otitis media (AOM). Using epidemiological data, we calculated the cases of IPD, PNE, and AOM, using country-specific incidence, serotype coverage, disease sequelae, mortality, vaccine effectiveness, indirect effects, costs, and utilities. Direct effects for PCV13- and PCV10-covered serotypes were assumed similar to PCV7. PCV13 was assumed to confer an indirect effect, while PCV10 was not. Assumptions were tested in sensitivity analyses. RESULTS: In a NIP, PCV13 was estimated to eliminate 31.7%, 46.4%, and 33.8% of IPD in Germany, Greece, and the Netherlands, respectively. Compared with PCV7 and PCV10, PCV13 was found to be cost-effective or cost saving in all cases when PCV13 indirect effects were included. CONCLUSIONS: Pediatric NIPs with PCV13 in Europe are expected to have dramatic public-health impacts and be cost-effective or cost saving.

[Aspects of outpatient palliative care and assessment of the nursing workload. Survey among care givers in Germany]. / Versorgungssituation von Palliativpatienten und Einschätzung der Arbeitsbelastung der Pflegenden. Befragung unter ambulant tätigen Pflegenden in Deutschland.

INTRODUCTION: The aim of this study is to explore aspects of the health care situation of outpatient palliative patients in Germany as well as effort and workload of care from the viewpoint of involved care givers. Additionally the future development with regard to the cooperation with other health care providers is assessed. METHODS: A detailed questionnaire was developed and sent to 188 outpatient care givers, all members of the German Association for Palliative Medicine, in January 2009. All data was analyzed via SPSS version 16. RESULTS: 69 questionnaires were included into statistical analyses. Care givers estimate the effort of care of palliative patients as very high. 28 per cent of working time is spent on administration. Responders consider general and quantitative workload to be the highest. Most care givers assess the SAPV-directive of the Federal Joint Committee as well as the future health care situation of palliative patients and cooperation with other health care providers as good. DISCUSSION: Further studies should focus on the collection of longitudinal patient data for a more comprehensive insight.