Thomas D. Szucs

European Healthcare Policies for Controlling Drug Expenditure

In the last 20 years, expenditures on pharmaceuticals — as well as total health expenditures — have grown faster than the gross national product in all European countries. The aim of this paper was to review policies that European governments apply to reduce or at least slow down public expenditure on pharmaceutical products. Such policies can target the industry, the wholesalers and retailers, prescribers, and patients.The objectives of pharmaceutical policies are multidimensional and must take into account issues relating to public health, public expenditure and industrial incentives. Both price levels and consumption patterns determine the level of total drug expenditure in a particular country, and both factors vary greatly across countries.Licensing and pricing policies intend to influence the supply side. Three types of pricing policies can be recognised: product price control, reference pricing and profit control. Profit control is mainly used in the UK. Reference pricing systems were first used in Germany and The Netherlands and are being considered in other countries. Product price control is still the most common method for establishing the price of drugs. For the aim of fiscal consolidation, price-freeze and price-cut measures have been frequently used in the 1980s and 1990s. They have affected all types of schemes. For drug wholesalers and retailers, most governments have defined profit margins. The differences in price levels as well as the introduction of a Single European Pharmaceutical Market has led to the phenomenon of parallel imports among member countries of the European Union. This may be facilitated by larger and more powerful wholesalers and the vertical integration between wholesalers and retailers.To control costs, the use of generic drugs is encouraged in most countries, but only few countries allow pharmacists to substitute generic drugs for proprietary brands.Various interventions are used to reduce the patients’ demand for drugs by either denying or limiting reimbursement of products and providing an incentive for patients to reduce their consumption of drugs. These interventions include defining a list either of drugs reimbursed (positive list) or one of drugs not reimbursed (negative list), and patient co-payments, which require patients to pay a proportion of the cost of a prescribed product or a fixed charge.Policies intended to affect physicians’ prescribing behaviour include guidelines, information (about price and less expensive alternatives) and feedback, and the use of budgetary restrictions.

Vaccination coverage rates in eleven European countries during two consecutive influenza seasons

OBJECTIVES This study assessed influenza vaccination coverage rates in eleven European countries during seasons 2006/07 and 2007/08. The aims were to analyse vaccine uptake rates in the general population and in high-risk groups, including children, as well as to understand the principal drivers and barriers towards vaccination. METHODS Community-based face-to-face interviews, telephone surveys or mailed surveys were conducted in UK, Germany, Italy, France, Spain, Austria, Czech Republic, Finland, Ireland, Poland and Portugal. Approximately 2000 representative adult individuals per country and season were interviewed. Data on the vaccination status of children were obtained by proxy interviews. For the analysis, five target groups were defined. RESULTS Vaccination coverage levels in the general population ranged from 9.5% (Poland) to 28.7% (UK) during season 2007/08. In comparison with the previous season, only minor increases were visible. The coverage in the elderly target group was highest at 70.2% in the UK and lowest at 13.9% in Poland. The vaccination rate of chronically ill persons ranged from 11.1% (Poland) to 56.0% (UK). Vaccination levels among health care workers were generally low. Vaccine uptake in children was lowest in Ireland (4.2%) and highest in Germany (19.3%). Respondents from all countries were aware of the seriousness of influenza as a disease. People who had never been vaccinated regarded being infected as unlikely. The advice from a family doctor or a nurse was deemed as the main encouraging factor for vaccination. CONCLUSIONS During 2007/08, influenza vaccination coverage rates differed widely between countries, not only in the general population but also in the predefined at-risk groups. Generally, the increases in coverage compared to the previous season were marginal. Overcoming the barriers and implementing the driving forces identified by our surveys may help to increase vaccine uptake and to reach the corresponding WHO goals.

Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons

BackgroundThe objectives of the survey were to identify the level of influenza vaccination coverage in five European countries between 2001 and 2007, to understand the drivers and barriers to vaccination, to assess vaccination intentions for the winter 2007/08 as well as major encouraging factors for vaccination.MethodsBetween 2001 and 2007, representative household surveys were performed with telephone or mailed (France) interviews of individuals aged 14 and above. The questionnaire used in the UK, Germany, Italy, France and Spain was essentially the same in all seasons. The data were subsequently pooled. Four target groups were defined for the analysis: 1) persons aged 65 years and over; 2) persons working in the medical field; 3) chronically ill persons and 4) combined target group composed of individuals belonging to one or more of the previous groups 1, 2 or 3.ResultsIn 2006/07, vaccination coverage was, 25.0% in UK, 27.4% in Germany, 21.8% in Spain, 24.2% in France and 24.4% in Italy. During six influenza seasons (2001–2007), vaccination coverage showed a slight positive trend in the five countries (p ≤ 0.0001). In the elderly (≥ 65 years), across all countries, no significant trend was seen; the vaccination rate decreased non-significantly from a peak of 64.2% in season 2005/06 to 61.1% in season 2006/07. The most frequent reason for getting vaccinated was a recommendation by the family doctor or nurse (51%), and this was also perceived as the major encouraging factor for vaccination (61%). The main reason for not getting vaccinated was feeling unlikely to catch the flu (36%).ConclusionIn the UK, Germany and Spain, influenza vaccination coverage rates in season 2006/07 dropped slightly compared to the previous season. However, a trend of increasing vaccination coverage was observed from 2001/02 to 2006/07 across Europe. The family doctor is the major source of encouragement for individuals getting vaccinated. Efforts to overcome the barriers to vaccination need to be put in place to reach the WHO objective of 75% coverage in the elderly by 2010. This is a major challenge to be faced by governments, healthcare workers and healthcare organisations.

Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans

The history of pandemic influenza, along with the evolving epizootic of the highly pathogenic avian influenza A (H5N1) virus and the severity of associated human infections, serve as a warning to the world of the threat of another influenza pandemic. Conservative estimates suggest that up to 350 million people could die and many more would be affected, causing disruption to health-care systems, society, and the worlds economy. WHO has encouraged countries to prepare in advance by developing influenza pandemic preparedness plans that involve public-health and pharmaceutical interventions. Vaccination is a cornerstone of these plans; however, a pandemic vaccine cannot be manufactured in advance because the next pandemic virus cannot be predicted. The concepts of vaccine stockpiling and prepandemic vaccination have thus become attractive. Human H5N1 vaccines are currently available and can induce heterotypic immunity. WHO and governments should give urgent consideration to the use of these vaccines for the priming of individuals or communities who would be at greatest risk of infection if an H5N1 influenza pandemic were to emerge.

Influenza vaccination uptake and socioeconomic determinants in 11 European countries.

BACKGROUND The objective of this study was to assess the predictive effects of socioeconomic factors to explain influenza vaccination coverage rates in 11 European countries. METHODS Data from national household surveys collected over up to seven consecutive seasons between 2001/2002 and 2007/2008 were analyzed to assess the associations of socioeconomic factors with immunization against influenza. RESULTS In total, data from 92,101 household contacts representative for the national non-institutionalized population aged above 14 years were analyzed. Influenza vaccination coverage rates in Europe remain suboptimal with little or no progress in the last years. The results of this study indicate that gender, household income, size of household, educational level and population size of living residence may significantly contribute to explain chances of getting immunized against influenza apart from the known risk factors age and chronic illness. The effect of these socioeconomic factors was differently expressed among the countries and could not be explained solely on basis of economic characteristics of these countries. CONCLUSIONS Future measures should address inequalities to achieve the WHO target by 2010 with an influenza vaccination rate of 75% in the elderly. National vaccination campaigns may need to take socioeconomic segments of the population here identified as less likely of getting the influenza vaccine into account.

Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: An economic evaluation

The addition of bevacizumab to weekly paclitaxel as primary chemotherapy for HER-2 negative metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase of toxicity. A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the E2100 clinical trial. Direct costs were assessed from the perspective of the Swiss health system. The addition of bevacizumab to weekly paclitaxel is estimated to cost an additional 40,369euro and to yield a gain of 0.22 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of 189,427euro/QALY gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of 60,000euro was never reached. The addition of bevacizumab to paclitaxel in MBC patients is expensive given the clinical benefit in terms of QALYs gained.

Disparities in influenza vaccination coverage rates by target group in five European countries: Trends over seven consecutive seasons

Background:The primary objective of this study was to measure influenza vaccination coverage rates in the general population, including children, and in high-risk groups of five European countries during the season 2007/2008. An additional aim was to analyze coverage trends over seven consecutive seasons and to gain an understanding of the primary drivers and barriers to immunization.Methods:Community-based telephone and mail surveys have been conducted in the UK, Germany, Italy, France, and Spain, yearly, since 2001/2002. Approximately 2,000 individuals per country and season were interviewed who were considered to be representative of the adult population aged 14 years and older. Data on the vaccination status of children were obtained by proxy interviews. The questionnaire used was essentially the same for all seven seasons. Five target groups were identified for the study: (1) persons aged ≥ 65 years; (2) elderly suffering from a chronic illness; (3) patients suffering from a chronic illness; (4) persons working in the health care sector; (5) children.Results:In the season 2007/2008, vaccination coverage rates in the general population remained stable in Germany. Compared to the coverage rates of the previous season, increases of 3.7%, 2.0%, and 1.8% were observed for the UK, Spain, and France, respectively, while a decrease of –1.5% was observed for Italy. Across all five countries, vaccination rates in the predefined target groups decreased to some extent (elderly) or increased slightly (chronically ill and health care workers). Vaccination rates among children varied strongly between countries and ranged from 6.1% in UK to 19.3% in Germany. The most powerful motivation for getting vaccinated in all countries was advice from a family doctor (58.6%) and the perception of influenza as a serious illness (51.9%). The major reasons why individuals did not become vaccinated were (1) the feeling of not being likely to catch influenza (39.5%) and (2) never having considered the option of being vaccinated (35.8%).Conclusions:The change in general influenza vaccination coverage in the 2007/2008 season compared to the previous season was small, but decreases were seen in some target groups. The underlying motivations for and against vaccination did not substantially change. An effort to activate those driving forces that would encourage vaccination as well as dealing with barriers that tend to prevent it may help enhance coverage rates in Europe in the future.

Multivariate analysis of febrile neutropenia occurrence in patients with non-Hodgkin lymphoma: data from the INC-EU Prospective Observational European Neutropenia Study

Myelosuppression, particularly febrile neutropenia (FN), are serious dose‐limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony‐stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non‐Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0–3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required.

Influenza Vaccination Coverage Rates in 5 European Countries: a Population-Based Cross-Sectional Analysis of the Seasons 02/03, 03/04 and 04/05

Introduction:Influenza continues to be a considerable health problem in Europe. Vaccination is the only preventive measure, reducing mortality and morbidity of influenza in all age groupsObjectives:The objective of this survey was to assess and compare the level of influenza vaccination coverage during three consecutive influenza seasons (02/03, 03/04, 04/05) in the five European countries United Kingdom, France, Italy, Germany and Spain, understand the driving forces and barriers to vaccination now and 3 years ago and determine vaccination intentions for the following winter.Methods:We conducted a random-sampling, telephone-based household survey among non-institutionalized individuals representative of the population aged 14 and over. The surveys used the same questionnaire for all three seasons. The data were subsequently pooled. Four target groups were determined for analysis: (1) persons aged 65 and over; (2) people working in the medical field; (3) persons suffering from chronic illness and (4) a group composed of persons aged 65 and over or working in the medical field or suffering from a chronic illness.Results:The overall sample consisted of 28,021 people. The influenza vaccination coverage rate increased from 21.0% in season 02/03 to 23.6% in season 03/04 and then to 23.7% in season 04/05. The differences between the seasons are statistically significant (p = 0.01). The highest rate over all countries and seasons had Germany in season 04/05 with 26.5%, Spain had in season 02/03 with 19.3% the lowest rate totally. The coverage rate in the target group composed of persons aged 65 and over or working in the medical field or suffering from a chronic illness was 49.7% in season 02–04 and 50.0% in season 04/05. The driving forces and barriers to vaccination did not change over the years. The most frequent reasons for being vaccinated given by vaccines were: influenza, considered to be a serious illness which people wanted to avoid, having received advise from the family doctor or nurse to be vaccinated and not wanting to infect family and friends. Reasons for not being vaccinated mentioned by people who have never been vaccinated were: not expecting to catch influenza, not having considered vaccination before and not having received a recommendation from the family doctor to be vaccinated. Options encouraging influenza vaccination are: recommendation by the family doctor or nurse, more available information on the vaccine regarding efficacy and tolerance and more information available about the disease. The adjusted odds ratio of receiving influenza vaccine varied between 2.5 in Germany and 6.3 in the United Kingdom in any risk group.Conclusion:The vaccination coverage rate increased from the first season (21.0%) to the third season (23.7%) by 2.6%. The family doctor is the most important source of encouragement for people to be vaccinated against influenza. It seems that the public would be more likely to be vaccinated if they had more information on the efficacy and tolerance of the vaccine, as well as the disease. We therefore suggest that family doctors be better informed on influenza vaccine and the disease itself, so that they can actively inform their patients on these topics.

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. Clin Cancer Res; 17(19); 6338–46. ©2011 AACR.