The analysis of cost-effectiveness of the optimal system of the blood service. University of Tartu

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1 The analysis of cost-effectiveness of the optimal system of the blood service University of Tartu Tallinn 2012

2 The analysis of cost-effectiveness of the optimal system of the blood service 2 Research ordered by Ministry of Social Affairs. Research done by University of Tartu. Authors of the research: Janika Alloja, University of Tartu Kerly Espenberg, University of Tartu Raul-Allan Kiivet, University of Tartu Authors of the research thank everybody who participated in the making of this report, including by assisting the project team in collecting data, found time for sharing experience in interviews and contributed in the development of solutions.

3 The analysis of cost-effectiveness of the optimal system of the blood service 3 TABLE OF CONTENTS Table of contents... 3 Short summary Introduction Focus of the report and research questions Methodology Terms used in the report Main components of blood and vein-to-vein chain Overview of blood services and developments Different blood services in developed countries Blood service in the UK Blood service in Finland Blood service in Sweden Trends in collecting, testing, processing and using blood products in Europe Blood service in Estonia Structure of Estonian blood service System of Estonian blood centres System of hospital blood banks Information system of blood service Donation in Estonia today and in the future Trends in donation Age-specific structure and residence of donors Collecting donor blood Forecast of the number of donors Evaluation to donation Use of blood products in Estonia Trends in the use of blood products in Estonia and the users of blood products Practice of blood product use Efficiency of using donor blood Sufficiency and availability of blood products Estimation of the use of blood products for years Evaluation to the use of blood products Quality of blood products Content of the quality and quality requirements for blood products in Estonia Content and organization of supervision by the State Agency of Medicines Self-control and training Safety of blood products and haemovigilance in Estonia Evaluation to blood product quality Economic efficiency of blood service Costs and structure of costs of the blood service Income of blood centres Productivity and unit price in blood centres Evaluation of economic efficiency General evaluation and recommendations Critical needs Recommendations Scenarios describing blood service division of responsibilities... 76

4 The analysis of cost-effectiveness of the optimal system of the blood service Scenario 1: maintaining current division of responsibilities Scenario 2: consolidating processing and testing Scenario 3: centralized (national) blood service with two blood centres Scenario 4: centralized (national) blood service with one blood centre Sensitivity analysis of the financial impacts of the scenarios Conclusion Sources Annexes... 96

5 The analysis of cost-effectiveness of the optimal system of the blood service 5 SHORT SUMMARY The focus of the research is the current situation, future outlooks and economic efficiency of Estonian blood service. In this analysis, cost-effectiveness marks a situation, where the same costs can provide more or better quality blood products, or products of same amount and same quality with less costs. The blood system is observed as a whole: from donation, processing and distribution to transfusion. The report is based on scientific literature, previous researches, expert interviews and analysis of statistic data. The research was conducted by University of Tartu and ordered by the Ministry of Social Affairs. The task of the blood service is to ensure the constant supply of safe blood products to healthcare institutions. As of 2012, there are four blood centres and 27 hospital blood banks in Estonia, which are all structural units of hospitals under private law and their division of responsibilities and cooperation is ensured by legislation and mutual agreements. In Estonia, blood service is financed from the budget of Estonian Health Insurance Fund through the prices set for blood products, in 2011 the whole cost of Estonian blood service was 5.8 million Euros. In a general evaluation to the situation of the blood service today, it can be stated that Estonian blood service is based on a relatively stable base of donors, in which a well functioning everyday blood product supply chain has developed and the safety of blood products is ensured. There is also a clear division of responsibilities and liability in order to ensure to function of everyday orders. The work of blood centres is efficient from the aspect of using donor blood and resources. Considering future developments and the limited resources in Estonia, the critical needs vitally important to implement are brought out in the report from the aspect of optimizing the further development and cost-effectiveness, and also recommendations, which should be considered. The three critical needs to ensure consistent blood supply are: - Moving from first-time and young donors to regular donors; - Developing a uniform blood service information system, which is important for optimizing costs, cooperation and safety; - Re-organizing the financing of blood service to help ensure the quality and safety. Three recommendations to support the development of blood service are: - Centralizing and systematically forwarding of the information necessary for donors; - Establishing central coordination, management and planning; - Deciding on the use of inactivated blood products on a national level. Three scenarios are brought out regarding the future of Estonian blood service, which differ on the levels of cooperation and consolidation. Compared to the current system, the changes would lead to an increase in cost-effectiveness by centralizing the processing and testing of blood products and implementing a unified information system for the blood service, which involves both donation and hospital blood banks. The supplementary cost-effectiveness is achieved through minimizing the future investment needs, with the prerequisites of agreements between hospitals and changes in financing blood products.

6 The analysis of cost-effectiveness of the optimal system of the blood service 6 1. INTRODUCTION The principle, that every country should be self-sufficient by using voluntary free donation, was set by the European Commission already in 1989 (European Commission Directive 98/381/EC). The Directive emphasizes the critical importance of the safety of blood transfusion. Therefore, the state must ensure a sufficient amount of safe blood products relying on its own donors. As blood is a biological product, that can be collected from donors only in a limited amount and cannot be kept as a supply, the efficiency of using blood is very important. This aspect becomes even more topical, since the demand for blood increases and supply of blood decreases due to the aging population and the requirements of qualifications for donors become stricter. In the context of limited resources increasingly more attention is paid on the cost of processing and economic analysis together with the efficiency of the use of blood products. The general concept in the economic analysis is ensuring efficiency, but the latter term is used very differently 1. Efficiency can be evaluated by comparing inputs and achieved health effects, which is done in cost-effectiveness analysis and used when comparing different health interventions. Alternatively, efficiency can be considered as the analysis of inputs and outputs through productivity and unit cost analysis. Analysis of planning the locations of blood centres and logistics is also closely related to efficiency (e.g. Sahina et al 2007, Sarul 2009, Nagurney et al 2012), also analysis of inventory management, matching demand and supply of blood products, analysis of waste minimization (e.g. Katsaliaki 2008), and analysis of productivity and scale effect (e.g. Bell et al 2008, Pereira 2006, Pitocco 2005, Veihola 2008). The system of Estonian blood service has been evaluated in three documents in the last years, which all focus on pointing out problems and offering solutions, but unlike the research at hand, they have not been focused on the aspect of economic efficiency. In the Transfusiology development plan (2001) it was stated after analysing the work of blood centres, that Estonian blood service is excessively fragmented. The processing capacities of smaller centres exceed the district s needs and fragmented blood processing limits the optimal use of donor blood. In the area of blood safety, it is brought out that blood testing is also fragmented causing difficulties in developing unified requirements and it is harder for smaller centres to ensure good processing practices and maintain quality. Depreciated facilities and equipment as well as complicated logistics also make it difficult for all centres to have good processing practices. Centralizing the blood service was seen as a solution for these problems, which would be based on two blood centres handling the processing and testing and one additional centre for donor management and storage. 1 In English literature the terms effectiveness, efficiency, technical efficiency etc are sometimes used in different meanings, hence the need to carefully observe what is measured in every specific case.

7 The analysis of cost-effectiveness of the optimal system of the blood service 7 Matra project 2 was conducted by Dutch experts in 2003 and mainly focused on three areas: developing a unified quality management system, developing a unified blood information system and raising awareness of the population and donors. The structure of the blood service was slightly mentioned as well, by stating that only North Estonia blood centre works with a sufficient processing capacity from the aspect of efficiency. The authors recommend considering one national blood supply organization in Tallinn, which would handle all the processing and testing and would have a supportive centre in Tartu for donor management, storing and distributing blood products and training. State program of developing blood donation and blood product self-sufficiency for brings out the most important problems in the area of donation and blood product supplying and offers measures for solving those problems. The highlighted problems are: 1. Insufficient level of blood donation, caused by the lack of awareness of the population and acknowledgment of the necessity of donation; 2. Lack of preparedness for nation-wide crisis situations; 3. The need for further development of blood product safety, which blood centres do not have resources for; 4. Complications of self-supplying with plasma products; 5. Depreciated facilities of PERH Blood Centre; 6. Inefficiency of small blood centres; 7. Shortfalls in developing the blood information system due to the lack of extra resources in blood centres. Until now, the costs of blood centres have not been aggregated and analysed, and this report is going to fill that gap Focus of the report and research questions The aim of the analysis is to offer the most optimal nation-wide model for developing blood donation and self-supplying with blood products in Estonia from the aspect of cost-effectiveness, which would be based on the current system and take possible future developments into consideration. Objective information about the Estonian blood service will be gathered in order to evaluate the current situation of the blood service and point out the problematic areas. The evaluation is based on the main goal of the state blood service to offer a sufficient amount of safe blood product. The sufficiency of blood products depends on two main factors the number of donors and the use of blood products. As blood products have a short shelf life, it is not possible to keep them in store for a long time hence the strategic supplies are based on the existence of donors. The larger the number of donors in a country and the more often they donate, the better it is ensured to have a supply of different blood types and blood products. The transfusion of blood products is also important the more optimal the use of blood products for transfusions, the more optimal is the use of donated blood. The safety of blood products depends on the epidemiologic situation of the country and the quality of blood processing and testing. 2 The aim of the Matra program was to support the implementation of legislation of the non-economic sector in European Union candidate states and creating lasting contacts between institutions of Netherlands and Estonia. The project Development of the Capacity of the Estonian Blood centres was a part of the program.

8 The analysis of cost-effectiveness of the optimal system of the blood service 8 The mentioned areas are closely related to efficiency of resource use. Therefore, the Estonian blood service will be evaluated through the following four areas. 1. Blood donation Are there enough donors (also compared to other countries)? How will the number of donors change in the near future? What are the problems of the current system from the aspect of blood donation? 2. Use of blood products Who are the users of blood products and what is the practice of using blood products (also compared to other countries)? How will the use of blood products change in the near future? Is the use of donor blood efficient (also compared to other countries)? What are the problems of the current system from the aspect of ensuring sufficient supply according to the need for blood products? 3. Safety of blood products What affects the quality of blood products? Are blood products safe? What are the problems of the current system from the aspect of blood safety? 4. Economic efficiency of the blood service How efficiently do blood centres use their resources (also compared to other countries)? Does the economic efficiency of blood processing depend on the capacity of processing? What are the problems of the current system from the aspect of economic efficiency? The evaluation of Estonian blood service is mainly based on the performance and work process of blood centres, but where possible and necessary, matters regarding hospital blood banks will also be handled. Based on the evaluation and the main problems highlighted during the analysis, the last chapter will propose activities which should or could be undertaken for developing the blood service. In addition, different scenarios describing the tasks for blood centres with an impact analysis has been brought out. In this report, blood service cost-effectiveness means a situation where 1) more products and/or products with better quality can be provided with the same costs or 2) the same amount and same quality products can be provided with less costs Methodology To gather necessary information for evaluating Estonian blood service and making suggestions, the relevant scientific and specialized literature, previous evaluations and other documents concerning Estonian blood service were consulted, experts were interviewed and other relevant data about important indicators in blood centres and on state level were gathered. Wherever possible, statistics about foreign countries was also obtained for comparison. In the analysis of scientific literature, attention was given to articles which focused on measuring and evaluating the efficiency of blood centres and blood service, forecasting the use of blood products in

9 The analysis of cost-effectiveness of the optimal system of the blood service 9 other countries and describing global developments. Additionally, information about blood services in other countries was searched, in cases of countries with centralized blood systems, valuable information was obtained from annual reports (e.g. Finland, Canada, the UK, Australia, New Zealand). In order to learn about the developments in Estonian blood service previous overviews (e.g. Transfusiology development plan and the state program of developing blood donation and self-supplying with blood products) and the legislation regulating the work of Estonian blood service were used. Main sources of information were interviews with various experts; 15 different experts were interviewed during the research. Heads of blood centres, head and specialist of the department of biologicals of the State Agency of Medicines, manager of treatment financing service of Estonian Health Insurance Fund were repeatedly consulted. Estonian Anaesthesiologists Association and Estonian Haematologists Association were asked for expert opinions about the forecast of the future use of blood products. Project manager of the Estonian blood service information system from Gennet Inc. was consulted to get acquainted to the information system of Estonian blood service. Representatives from hospital blood banks from three hospitals were interviewed about the work of hospital blood banks. Experts from the blood services of the UK, Finland and Sweden were contacted for information about blood services in their countries. In addition to the information from the interviews, different numeric data was gathered for an objective overview of the blood service. Data about staff, donors, blood donations, mobile collections, processing capacities etc was asked from blood centres. In addition, detailed financial reports from , list of equipment and a list of issued products of 2011 were received. Blood centres also enabled access to their information systems for statistics of donors by age and residence. Statistics on state level was received from two sources. Firstly, from the database of health statistics and research of the National Institute for Health Development (TAI), where various indicators from annual reports of blood centres and also the information submitted by hospitals about the use of blood products and cases of transfusion reactions are aggregated. Secondly, aggregated data about compensated blood products in and detailed data from by hospitals from Estonian Health Insurance Fund. Estonian Health Insurance Fund also provided an overview of the model of product prices, which includes information about the costs calculated in the product prices. Main information sources describing blood supply in foreign countries were the European Directorate for the Quality of Medicines & Healthcare (EDQM) annual reports about blood collection, processing and testing in European countries. Several analyses were performed based on the collected data: Analysis of donors by age and residence and the forecast of the number of donors based on the population projections; Analysis of trends in the use of blood products and comparison two datasets the statistics of compensated products by the Estonian Health Insurance Fund and the statistics of the use of blood products by the TAI submitted by hospitals; Analysis of users of blood products by healthcare providers, types of providers and counties based on the data from Estonian Health Insurance Fund; Analysis of practices of blood product use by larger hospitals, comparison with other countries; Analysis of efficiency of donor blood use, during which all the losses from collecting donor blood to transfusion in every stage of the process were calculated, comparison with other countries; Gathering financial reports of blood centres for comparing and grouping costs, comparison with other countries;

10 The analysis of cost-effectiveness of the optimal system of the blood service 10 Calculation and analysis of productivity and unit price by blood centres, comparison with other countries; Comparing equipment in blood centres and calculating the proportion of equipment, which has exceeded optimal period of use; Calculating sales revenue of blood centres based on the product prices and number of issued blood products, comparison of results with the sum compensated by Estonian Health Insurance Fund; Grouping the costs of blood centres by stages of the production chain, according to the price model of Estonian Health Insurance Fund; Assessing financial impacts of scenarios describing possible division of responsibilities in blood service Terms used in the report Aphaeresis a procedure, during which one or several components of blood are separated from the whole blood and the residual components of the blood are transfused back to the donor during or at the end of the procedure (European Commission Directive 2004/33/EC). Aphaeresis platelets concentrate blood product containing the platelets of one donor suspended in blood plasma or additive solution and anti-coagulation solution obtained by aphaeresis (Procedure of using blood preparations at Tartu University Hospital). Blood centre an independent healthcare provider or a hospital department, with the tasks to collect blood and produce, examine, store and issue blood components with the aim to guarantee the availability of blood components to healthcare providers. Blood component a therapeutic constituent of blood e.g. erythrocyte, platelet, plasma (European Parliament and Council Directive 2002/98/EC). Blood plasma a non-cellular component of blood transporting blood cells, nutrients and residues and participates in coagulation. Blood product a therapeutic product derived from human blood, which contains one or several components of blood (European Parliament and Council Directive 2002/98/EC). The Blood Act uses the term blood preparation which is medication produced from blood and packaged and marked accordingly, containing one or several components of blood. Blood preparations are whole blood, blood components and plasma derivatives. Blood service the system of blood centres and hospital blood banks in a state. Buffy coat blood component prepared by centrifugation of a unit of whole blood, which contains a considerable proportion of leucocytes and platelets (European Commission Directive 2004/33/EC). Buffy-coat (BC) platelets concentrate concentrated suspension of blood platelets obtained by processing whole blood units and pooling the derived platelets (European Commission Directive 2004/33/EC). According to the number of pooled units, 1BC, 2BC, 3BC, 4BC and 5BC platelets concentrates are recognized.

11 The analysis of cost-effectiveness of the optimal system of the blood service 11 Cross-matching an activity during which the donor blood compatibility for a recipient is analysed and the suitable donor blood is identified for a recipient. Cryoprecipitate blood product prepared by concentrating fresh frozen plasma and containing important plasma proteins participating in the coagulation process (Procedure of using blood preparations at Tartu University Hospital). Donation i.e. giving blood one-time blood donation. Donor a person with active legal capacity, who is years of age and donates blood for the purpose of treatment of other persons to a handler of blood (Blood Act). Erythrocyte i.e. red blood cell cellular component of blood carrying oxygen to the tissues and organs of a body. Erythrocyte suspension blood product containing erythrocytes suspended in anti-coagulation and nutrition solution (Procedure of using blood preparations at Tartu University Hospital). Filtration procedure where leucocytes are removed from the blood product by a leucocyte removal filter. Fractionation industrial process where different components are separated from blood plasma to prepare plasma derivatives. Fresh frozen plasma blood product separated from whole blood by centrifugation or collected by aphaeresis and frozen. Haemovigilance the procedures of reporting and identifying the causes of serious adverse events occurring during collection, testing, processing, storage and distrubution and serious adverse reactions occurring during or after blood transfusion (Blood Act). Hospital blood bank structural unit of a hospital with the tasks to order and storage blood components and distribute them within the hospital, perform immunohematological testing and coordinate and advise the use of blood component transfusions for treatments. Immunohematological testing tests where the ABO and Rh(D) type, K-antigen and irregular antibodies are identified and/or the crossmatch of recipient and donor blood is performed. Irradiation procedure where the ability of lymphocytes to proliferate in blood products can be inhibited with ionized radiation (Procedure of using blood preparations at Tartu University Hospital) NAT-test (nucleic acid test) molecular biology test for directly identifying pathogens DNA or RNA in blood, which enables to identify viruses with shorter window period compared to serological tests, which indentify antibodies in blood. Pathogen inactivation/reduction procedure with blood products where nucleic acid replication is disabled and therefore viral infections and bacteria are inactivated in blood products. Plasma product i.e. plasma derivative medication industrially produced from the blood plasma of several donors and includes a certain component of blood plasma, e.g. albumin (Blood Act).

12 The analysis of cost-effectiveness of the optimal system of the blood service 12 Platelet i.e. thrombocyte cellular component of blood which participates in coagulation process. Recipient a person on whom a blood transfusion is performed (Blood Act). Reconstituted blood blood product prepared by pooling erythrocytes and fresh frozen plasma (Procedure of using blood preparations at Tartu University Hospital). Retrospect procedure an act initiated to identify the causes of serious adverse events or side effects that happened during the process of handling blood in order to identify a recipient to whom a potentially infectious blood component was transfused, or a donor, whose donated blood was the source of the blood component transfused to the patient (Haemovigilance and blood component recall conditions and procedures). Serious adverse event untoward occurrence associated with the collection, testing, processing, storage and distribution of blood and blood components, which might lead to death or life-threatening, disabling or incapacitating conditions for patients, or which results in, or prolongs, hospitalization or morbidity (European Parliament and Council Directive 2002/98/EC). Serious adverse reaction unintended reaction on a donor or a recipient associated with the collection or transfusion of blood or blood component, which is fatal, life-threatening, disabling, incapacitating, or results in, or prolongs, hospitalisation or morbidity (European Parliament and Council Directive 2002/98/EC). The term transfusion reaction is also used to describe a serious adverse reaction on a recipient. TRALI (transfusion related acute lung injury) lung injury occurring during or after blood transfusion, which can be fatal. Transfusion therapy or blood transfusion medical procedure where the recipient is transfused whole blood or blood components (Blood Act). Virus testing tests, where donor blood is examined for pathogens, e.g. pathogens for HIV, hepatitis and syphilis. Washed red cells process of removing plasma or storage medium from cellular products by centrifugation, decanting of the supernatant liquid from the cells and addition of an isotonic suspension fluid, which in turn is generally removed and replaced following further centrifugation of the suspension. The centrifugation, decanting, replacing process may be repeated several times. (European Commission Directive 2004/33/EC). Whole blood blood taken from a donor containing all blood component (term is also used for single blood donation in European Commission Directive 2004/33/EC). Also unprocessed donor blood in anticoagulation and nutrition solution (Procedure of using blood preparations at Tartu University Hospital) Main components of blood and vein-to-vein chain In modern medicine, blood products instead of whole blood are used for transfusion, in order to save donor blood and avoid the use of blood products not necessary for the treatment of a specific patient.

13 The analysis of cost-effectiveness of the optimal system of the blood service 13 Blood products are made by separating blood components from whole blood - every component has a different function. Erythrocytes help to transfer oxygen into blood. Erythrocyte suspension is produced from erythrocytes, which is used to treat anaemia and in cases of extensive blood loss due to trauma or surgeries. Platelets help blood coagulate. Platelet concentrate is produced from platelets, which is used for treatments of blood diseases (including leukaemia) and other diseases which interfere with blood coagulation. Plasma is used to treat coagulation disorders. Fresh frozen plasma and cryoprecipitate are produced from plasma. Plasma products (e.g. albumin, immunoglobulins, coagulation factors) are prepared from pouring together plasma from several donors. Plasma products are used for several diseases, e.g. immune deficiency, neurological-, infectious- and autoimmune diseases, heart failure, asthma, repeated miscarriages, bleedings and haemophilia. The process from collecting donor blood to transfusion of blood products can be divided into five stages 1) collecting blood from donors, 2) producing blood products, 3) testing, 4) storing and distributing to hospitals and 5) transfusion. The first four stages are performed in blood centres, the fifth in hospitals (q.v. Figure 1). Blood centre Processing Collecting Testing Storing and distribution Donors Loss - defects - infections - expiration Hospitals Transfusion Figure 1. Scheme of the process of blood movement COLLECTING Blood can be collected as whole blood donations and via aphaeresis. During whole blood donations, the donor is taken 450 millilitres of blood, which is called a whole blood dose. With aphaeresis, one or several components of blood are separated and the rest of the blood is transfused back to the donor during or after the procedure. This enables to collect a larger quantity of a specific component, for example 1-3 doses of platelets concentrates during aphaeresis, or several components at once, like one dose of platelets and two doses of plasma.

14 The analysis of cost-effectiveness of the optimal system of the blood service 14 TESTING Blood testing begins in the phase of collection, where the donor is taken an extra 20 millilitres of blood. This is used for immunohematological testing of the donor blood (identifying the blood type and antibodies) and identifying viral infections. Infections can be identified only after the so-called windowperiod, which differs by infections. PROCESSING The collected whole blood is separated into blood components during processing. For this, the dose of whole blood is put in centrifuge, which separates the components into layers by their weight. Then the layers of plasma, erythrocytes and the layer of platelets and leucocytes are separated in the separator. As for the latter, the amounts of 3-4 doses of the same blood type are pooled together and the leucocytes are separated by centrifuge producing a platelets concentrate. In addition to separating blood components from whole blood, different procedures can be performed to clean erythrocytes and platelets in certain manners. washing erythrocytes are washed three times with a physiological solution, which removes a large amount of leucocytes and platelets in addition to plasma proteins; filtration an erythrocyte suspension is poured through a special filter to remove the leucocytes; irradiation for further removal of leucocytes, the blood product is irradiated with ionized radiation, which disables the lymphocyte ability to proliferate while not harming the erythrocytes and platelets. Plasma is processed into more than 20 different blood products through cleaning, concentrating and removing different components i.e. fractionation. STORING Blood components are stored in different temperatures. Plasma is stored in a fast-freezer after separation, where it has to be frozen into -30 degrees in an hour and it can then be stored up to 3 years. Erythrocytes are stored at +2 to +6 degrees and the cells are suitable for transfusion for 35 days. Platelets need room temperature and constant gentle shaking for survival. Platelets concentrate can be stored for 5-7 days. TRANSFUSION Blood centres issue blood products according to orders to hospital blood banks, where blood products are stored and issued for transfusions. The recipient s blood type is identified and matching i.e. analysis for the compatibility of the donor s and recipient s blood is performed for the transfusion. The recipient is transfused blood which matches their type or is 0-negative. If antibodies are identified in the recipient s blood during matching, the blood is sent to the blood centre for typing the antibodies and finding specific donor blood.

15 The analysis of cost-effectiveness of the optimal system of the blood service OVERVIEW OF BLOOD SERVICES AND DEVELOPMENTS The following chapter gives an overview of different systems of blood services and focuses in detail on the blood services in three countries Finland, the UK and Sweden. The countries are chosen by the different types of their blood services (accordingly: coordinated by the Red Cross, state system and a decentralized system). The current matters of blood products and blood processing, which could influence future developments, are brought out in the end of the chapter Different blood services in developed countries Different countries have introduced different blood service systems, some of them centralized i.e. under unified management, others decentralized (q.v. Table 1). In decentralized systems, several organizations collect and process blood, e.g. hospitals in Norway and Sweden. In centralized systems the blood service system is coordinated by the Red Cross or the state. In most cases the systems are non-profitable, however some countries also have profit-oriented centres. For example, The National Plasma Centres in the USA compensates donors for donating plasma. According to the data on the organization s website, there are over 500 profit-oriented plasma collection centres with million paid donors in the USA. Table 1. Blood service systems of the world Centralized National Centralized NPO (e.g. Red Cross) Decentralized Hospitals Mixed systems France The UK New Zealand Ireland Latvia Finland Netherlands Australia Switzerland Canada Austria Germany Norway Sweden Estonia Denmark USA (Red Cross + America s blood centres (network of indep. non-profit community blood centres) Lithuania (National blood centre + two hospital-based blood centres + one profit-based blood centre) Source: European Blood Alliance, Veihola 2008, websites of blood centres Centralized blood systems are more common in Europe and other developed countries and according to the South and East European Network, European countries move towards centralized blood service systems due to the increasing requirements for the safety and quality of blood products and the increasing costs of blood processing (SEEHN, WHO, Current Status and Future, 2011). For example, such developments have occurred in the UK during the last twenty years (q.v. chapter 2.1.1). Both centralized and decentralized blood systems have strengths and weaknesses. The strengths of centralized systems are: possibility to concentrate more sophisticated activities into fewer blood centres, which enables to achieve better quality and decrease costs; more optimal use of human and financial resources; better blood supply management between different regions; easier planning and adjustment of blood demand; easier standardization of blood centre activities (Moftah 2004). The World Health Organization (WHO) also brings out the advantages of centralized systems being unified planning and coordination and cost-effectiveness, but problems with logistics were mentioned. In decentralized

16 The analysis of cost-effectiveness of the optimal system of the blood service 16 systems the problems could occur with ensuring the unity of services, cost-effectiveness and quality management (WHO, Strategies for Safe Blood Transfusion, 2000). In addition to the level of centralization of management, another aspect giving information about a country s blood service is the number of blood centres. Generally countries with a larger population and area have more blood centres, but not always. For example, Finland has blood centres in 17 regions, but in Switzerland blood is processed in about 50 blood centres. Table 2. Number of blood centres and hospital blood banks in European countries, 2010 No. of blood establishments in a country No. of hospital blood banks in a country Austria 16 blood establishments, 14 plasmapheresis centres 150 Belgium Bulgaria 5 regional centres, 28 hospital-based smaller blood 56 collection departments Cyprus 1 6 Czech Republic Denmark 13 blood centres, 59 donation sites 61 Finland 1 blood establishment with 17 sites 54 France 17 regional establishments for processing and testing, 705 collection in 158 places and distribution in 152 Germany 84 blood establishments with 140 processing sites, 5 approximately 800 private organizations focused on plasma collection for fractionation Greece Ireland 5 55 Italy 326 Blood Transfusion Services with tasks of both 326 Blood Transfusion Services with tasks blood centres and blood banks of both blood centres and blood banks Liechtenstein 2 1 Lithuania Luxembourg 1 9 Malta 1 4 Netherlands 1 approximately 115 Norway 36 Some Poland Portugal 26 Romania 41 blood establishments, one blood establishment of 345 the Ministry of Defence Slovakia 44 unknown as are not registered Slovenia 3 blood establishments, one with 2 departments in 3 different locations. Other 7 blood establishments are becoming part of one existing centre. Spain Sweden 32 transfusion centres in 82 locations with tasks of 82 both blood centres and blood banks Switzerland 54 licenses for blood establishments, which perform approximately 100 collection and/or processing activities, 50 licenses for establishments which perform serology testing The UK Source: European Commission, Summary Table of Responses. (2010)

17 The analysis of cost-effectiveness of the optimal system of the blood service Blood service in the UK 3 Blood service in the UK (National Health Service Blood and Transplant, NHSBT) is a part of the national healthcare system, whose tasks are to ensure a supply of blood, organs and tissues and to improve the quality of blood and transplant services, productivity and economic efficiency. NHS organ donor registry, the British bone marrow registry and NHS cord blood bank are also located at the NHSBT. The blood service system consists of blood establishments, smaller blood collection clinics and mobile blood collection units. There are 15 blood establishments which work as distribution centres. Only three of them perform blood testing (microbiological and NAT-tests) and five perform blood processing. About half of NHSBT staff work in mobile blood collection units. 2 million doses of whole blood and doses of aphaeresis platelets were collected from 1.4 million blood donors in 2011/ million doses of erythrocytes and 0.27 million doses of platelets were produced. NHSBT receives its main income from the sales of blood products and services to hospitals. The prices of services and products are set annually via national commissioning process, based on the volume assumptions for the services and products provided for the year ahead and the prices are calculated so they would cover the operating costs. In addition, NHSBT receives income via central financing from the government, which is used to cover mostly the costs of special services and organ donor services. The latter also covers capital investments (e.g. purchase of equipment). In 2011/2012 NHSBT income was 431 million pounds, from which 72% came from sales revenue, the operating surplus was 4.3 million pounds. 6.5 million pounds (1.5% of the income) was set for capital investments. The blood system of the UK has been strongly centralized during the last twenty years. In the beginning of 1990s, 14 independent regional blood systems were reorganized and National Blood Authority was created. Until 2000, the system was divided into three competing zones. In 2000 another reorganization took place, where the zones where lost. In 2005 NHSBT was created. The new organization began consolidating processing and testing, as a result of which the number of processing and testing sites was planned to be decreased from twelve to eleven in 2007 to five and three by the end of The number of testing sites is planned to be decreased from three to two by March The main reason of consolidation was the need to raise the economic efficiency and quality in order to decrease the prices of blood products. In the period of 2008/ /12 the price of erythrocytes decreased from 140 pounds to 125, saving 30 million pounds. (NHSBT website, The National Audit Office Audit Report 2000, NHSBT Commercial Review 2011, NHSBT Strategic Plan , NHSBT Annual Review 2011/2012, Sandle (2011)) Blood service in Finland Finnish Red Cross blood service (FRCBS, Punainen Risti Veripalvelu) is the centralized non-profit unit of Finnish Red Cross. The main goals of FRCBS are to provide blood products to health care sector and to coordinate blood donation. FRBCS also offers the following services to hospitals: red cell serology testing; 3 NHSBT, i.e. the blood service of England and North Wales is under observation. In addition to the mentioned organization, there are also independent Northern Ireland Blood Transfusion Service, Welsh Blood Service and Scottish National Blood Transfusion Service in the UK.

18 The analysis of cost-effectiveness of the optimal system of the blood service 18 testing of organ, tissue, and stem cell transplants; testing and supplying with coagulation factors and platelets; management of Bone Marrow Donor Registry and Cord Blood Bank. FRCBS also works actively with R&D activities and consultations. The Finnish blood service is divided into 17 districts. The main operating site is located in Helsinki blood centre, where most of the laboratory analyses are performed. Additionally, there are four regional centres in the Finnish blood service (Kuopio, Oulu, Tampere and Turku) and 12 local donor centres. All sites collect donor blood, which gives approximately 60% of the collected donor blood, 40% of the donor blood is collected from mobile units and donor days held all over Finland. Blood testing, processing and distribution are centralized. Blood testing is concentrated into one centre. Blood processing is performed in two centres (Helsinki and Oulu, processing was stopped in Tampere) since Distribution of blood products is also done from two centres; under special conditions hospitals can also offer blood products to each other doses of blood (48.7 doses per thousand people 4 ) was donated in Finland in 2011 and 5000 doses of plasma and 500 doses of platelets were collected via aphaeresis doses of erythrocytes, doses of platelets and doses of fresh frozen plasma were produced from the blood (accordingly 44.4 doses, 7.8 doses and 9.3 doses per 1000 people) and transfused to patients. Plasma products (including Octaplas) are bought in outside the country, in addition to Octapharma, a contract was also made with Baxter in During three years, the amount of erythrocytes sold to hospitals has decreased (from in 2009 to in 2011) and the amount of platelets has increased (from to doses). Finnish blood service is not profit-oriented and their main income comes from the sales of blood products and services to hospitals, which is used to cover the operating costs and investments. FRCBS yearly income was 69 million Euros in 2011, 66% of which was received from the sales of blood products, 12% from the sales of unprocessed plasma and 9% came from laboratory tests. The largest costs were related to staff (48%) and materials and subcontracting (25%). The loss of 2011 was 2.3 million Euros, but the surplus of 2010 was 1.8 million Euros. The blood service does not receive financial aid from its rooforganization nor from the Finnish government. (FRCBS website, FRCBS Annual Report 2010 and 2011) Blood service in Sweden The Swedish blood system consists of blood centres managed by county councils. Sweden has 30 blood organizations (Blodcentralsorganisation), consisting of blood centres, donor centres and mobile blood collection units. Blood centres are mostly located at hospitals (81 hospitals), but blood is collected in separate stationary donor sites (e.g. shopping centres) and mobile units, with the total of 24 and 14 in Mobile collection units visit cities, counties and larger organizations. The internal division of responsibilities is decided by the blood organizations themselves. For example, at larger counties the blood centre at a university hospital is usually set as a regional blood centre, which is responsible for other blood centres located at smaller hospitals (e.g. unified quality systems, logistics of blood products etc). In several counties the regional centres are responsible of blood testing, processing or provision of specific blood products. 4 The information about Finnish population in 2011 found in the website of Statistics Finland is used for stating the collected blood and produced blood components per 1000 people ( people).

19 The analysis of cost-effectiveness of the optimal system of the blood service 19 Several organizations cooperate on state level. A non-profit organization Sweba created in 2004 by blood centres is the coordinator of the work of all blood centres. The main task of Sweba is to develop the electronic information exchange system between blood centres, but it also represents Sweden at European Blood Alliance. The Swedish Transfusion Medicine Association (Svensk Förening för Transfusionmedicin) has the central role in training transfusion medicine specialists and developing working standards. Several working groups, e.g. the working group of guidelines and haemovigilance working group belong to the association. Since 2005, the association also compiles reports gathering the main indicators of blood service. Information about donation is gathered in the national website geblod.nu, which also gives information about blood donation sites (including mobile collection sites) and blood supplies of blood centres. Sweden has about donors, from whom donated blood in 2011 (25 donors per 1000 people). There were first-time donors. In total, doses of blood was donated in 2011, with an average of 2 donations per donor doses of erythrocytes were produced, from which 97.5% were used for transfusions. On average, 51 doses of erythrocytes are transfused per 1000 people in Sweden doses of platelets were produced (5.3 per 1000 people), from which 70% were BC platelets. All the transfused platelets were leucocytes-free, 55% irradiated and 17% inactivated doses of plasma were transfused (24 tons), 141 tons of plasma was sent to fractionation. Blood centres receive their income from the sales of blood products and services and from selling plasma to fractionation. The budgets of blood centres are set by the hospitals, and the hospital budgets are confirmed by counties. The prices are set by blood centres so they would cover the costs. Blood centres do not receive additional financial support from the state. (Blodverksamheten i Sverige 2011, website of Swedish donation, website of Swedish Transfusion Medicine Association) 2.2. Trends in collecting, testing, processing and using blood products in Europe Statistics about the collection, use and safety of blood and blood products in European countries is gathered by European Directorate for the Quality of Medicines & Healthcare (EDQM). EDQM issues annual reports since In 2011 the first overview of European trends was issued, which aggregates information from Based on the analysis of data from , the report concludes (van der Poel et al 2011b): 1. Blood supplying in Europe is stable, the proportion of first-time donors and the number of donors and donations per inhabitant has not changed; 2. The use of erythrocytes has increased (0.4 doses per 1000 people); 3. The use of platelets has not changed, but the use of aphaeresis platelets has increased (1.7% per year); 4. The use of fresh frozen plasma has increased (0.3 doses per 1000 people per year); 5. Proportion of plasma going into fractionation has not changed; 6. Proportion of leukocyte depleted erythrocytes has increased, average of 4.3% per year; 7. No significant changes in using testing methods (information about serological and NAT-tests).

20 The analysis of cost-effectiveness of the optimal system of the blood service 20 Although according to the research of EDQM there have not been significant changes in the number of donors in , a risk factor for the future is the aging population. Potential donors are mostly year-olds, recipients mostly over 60. So the aging population in the Western world has two negative effects on donation the proportion of people in the appropriate age for donation is decreasing and the proportion of those in need of blood products is increasing. In Western societies, blood requirements have steadily increased over the past two decades, mainly due to developments in haematology and oncology and increasing numbers of major surgical procedures (Greinacher et al 2010). According to the prognosis of NHSBT, the need for erythrocytes in the UK increases 7% by 2021 and the need for platelets 34% (NHSBT, Strategic Plan , 2012). Drackely et al (2012) estimates blood deficit in Canada already by Several steps have been taken to avoid a deficit in blood products. One of the measures has been expanding the age limits for donation. For example, the UK, Australia and some states in the USA have removed the upper age limit for donations and in the UK, USA and some blood centres of Denmark have lowered the age limit to 17 (Ali et al 2010). Another step has been promoting a more optimal use of blood products i.e. minimizing discarded blood products and avoiding excessive transfusion. The European project EU Optimal Blood Use has developed a manual discussing several similar matters. Developing the safety of blood products is also constantly being worked on. Blood transfusion has to be as safe as possible for the patient, but unfortunately there is always the risk of side effects and virus transmissions. Viral infections are currently tested with NAT-tests (nucleic acids testing) and antibody tests, but due to the window-period and fact that only the most common viral diseases and virus subtypes are tested, the transmission of viral infections is not completely eliminated. Also, the mutation of viruses can also cause a situation, where the virus cannot be identified with the usual tests. From non-infectious complications, one of the most serious is TRALI (transfusion related acute lung injury), i.e. posttransfusion lung damage which can be fatal. In order to minimize the transmission of viral infections, stricter criteria for donor screening are used to try to achieve the safety of blood products. For example, the current matter is forbidding blood donation for people with certain sexual behaviour (MSM men having sex with men, European Commission, Joint meeting., 2010). Secondly, more sensitive tests and/or tests for new viruses are developed. For example, in addition to antibody tests, NAT-tests are used and avoiding West Nile virus is the current issue in Europe (European Commission, Joint meeting. 2010). Processing technologies are also under development to increase blood product safety. One of the possibilities to decrease the risk of viral transmissions due to the window-period is pathogen reduction i.e. pathogen inactivation in blood, which means that blood products are processed with specific extra subsistence in order to destroy all viral infections. Several methods have been developed for that, which are used on plasma and platelets. There is yet no efficient method for inactivating erythrocytes. Solventdetergent (SD) method used for plasma inactivation is believed to have an effect on reducing or eliminating the risk of TRALI as well, as the plasma of multiple donors is pooled during processing (AuBuchon 2011). There are no prospective studies, which have evaluated the incidence of TRALI after using inactivated plasma. However, there have been no reported cases of TRALI following the transfusions of Octaplas or other inactivated plasma products. In addition, a recent review of haemovigilance data from four different European countries (Fleshland 2007) reported no TRALI cases in Norway, where Octaplas is widely used, while in the three other countries where only fresh frozen plasma is used the incidence of TRALI was per doses (Membe et al 2011).