Supply and demand for hemophilia treatments-Systems-based approaches to mitigate the risk.

Treatment of hemophilia consists of replacement of the missing coagulation factor, either prophylactically or at the time of injury or bleeding. Because of the high cost of these products, which can present a barrier to care, different procurement strategies have been developed at national and regional levels. The emergence of novel therapeutic agents adds complexity to these strategies. This paper examines the benefits and challenges of these strategies, with primary reference to the Canadian context and a consideration of the concepts of value-based care.

Public expenditure for plasma-derived and recombinant medicinal products in Italy.

BACKGROUND: In Italy, the supply of plasma-derived medicinal products funded by the National Health Service can be through public healthcare facilities, accredited pharmacies or toll fractionation agreements between Regions and the manufacturer. Pharmaceutical public expenditure includes the supply related to the first two channels and costs can significantly vary because of channel-specific price reductions. This paper describes 2011 public expenditure for plasma-derived medicinal products purchased on the market, as well as the cost analysis per active substance. MATERIALS AND METHODS: Analysis of the usage of plasma-derived medicinal products and of the related expenditure in public facilities has been carried out using medicinal product traceability data. The analysis related to the accredited pharmacies channel has been carried out using quantities for every medicinal package recorded by Pharmacy Associations and applying reference prices in force on March 1(st), 2012 as well as discounts for the accredited pharmaceutical expenditure imposed by law. RESULTS: At national and regional level, total and total per capita expenditures on plasma-derived medicinal products by market channel and funded by the National Health Service are shown. Analysis was conducted considering the active substances in three groups: substances included in toll fractionation agreements, recombinant coagulation factors, and other substances not included in toll fractionation agreements. In 2011, the national expenditure estimate for plasma-derived and recombinant medicinal product acquisition on the market was about € 535 million. DISCUSSION: The purchased volumes and mean purchased prices per unit of each substance have a significant influence on the observed regional variability of the pharmaceutical public expenditure. A strategy of regional comparison aimed at both sharing a national range of reference for purchase prices and evaluating modalities for centralised purchasing is desirable.

Haemophilia: provision of factors and novel therapies: World Federation of Hemophilia goals and achievements.

For nearly 50 years, the goal of the World Federation of Hemophilia (WFH) has been to achieve 'Treatment for All' patients with inherited bleeding disorders, regardless of where they live. With proper diagnosis, management and care, people with bleeding disorders can live perfectly healthy lives. Without treatment, the reality is that many will die young or, if they survive, suffer joint damage that leaves them with permanent disabilities. Only about 25% of the estimated 400 000 people with haemophilia worldwide receive adequate treatment. The percentage is far lower for those with von Willebrand Disease (VWD) and the rarer bleeding disorders. The achievements of the WFH to close the gap in care for people with bleeding disorders are measureable over time by using three key indicators; the difference in the estimated and actual number of people known with bleeding disorders, the amount of treatment products needed versus that available, and the number of people born with bleeding disorders and the number who reach adulthood. There are five essential elements to achieve a sustainable national care programme: ensuring accurate laboratory diagnosis, achieving government support, improving the care delivery system, increasing the availability of treatment products, and building a strong national patient organization.

Primary prophylaxis in children with haemophilia.

Starting from the clinical observations that moderate haemophiliacs experienced only few bleeding episodes and rarely developed significant joint deterioration (haemophilic arthropathy), and the pioneer experience in Sweden, prophylaxis (i.e. the regular and long-term administration of clotting factor concentrate in order to prevent bleeding) has been practiced for more than forty years in severe haemophilia and is currently recommended as the first choice of treatment by the World Health Organisation and World Federation of Hemophilia and by many national medical/scientific organizations. Observational studies clearly established the superiority of prophylaxis over on-demand treatment in reducing the risk of arthropathy, also showing that starting prophylaxis earlier in life and after very few joint bleeds was associated with better joint outcomes, and led to the current definitions of primary (started before the age of 2 yrs and after no more than one joint bleed) and secondary prophylaxis. More recently, evidences from randomized trials, which were previously lacking in this setting, were also provided. This review summarizes available data from which current clinical practice of primary (and early secondary) prophylaxis in children with severe haemophilia was drawn. Open issues concerning optimal regimens and barriers to the implementation of prophylaxis are also discussed.

Factor replacement therapy in haemophilia--are there models for developing countries?

Successful models for factor replacement in severe haemophilia involves prophylactic or on-demand administration of large quantities (1500-9000 IU kg-1 year-1) of very high purity factor concentrates starting early in life. The prohibitive cost of these protocols make them completely impractical in developing countries where the quantity of factor used for replacement therapy is much lower and varies considerably (25-500 IU kg-1 year-1). At this level of treatment, as some joint damage is inevitable, the aim of therapy shifts to preventing disability and preserving reasonable joint function rather than perfect architecture. There are no carefully recorded data on long-term outcome of musculo-skeletal function on these doses. Appropriate studies are needed to document such data. With regard to products for factor replacement, economic compulsions lead to the use a variety of factor concentrates and blood-bank products for replacement therapy. Most patients in the developing world do not have access to adequate replacement therapy. Among the rest, some get limited quantities of plasma-derived concentrates while others use cryoprecipitate, fresh frozen plasma or even whole blood. Since the superiority of virus-inactivated purified factor concentrates in achieving the aims of replacement therapy is well established, the aim should be to provide this for all people with haemophilia. This can be achieved by production of such concentrates locally or by importing them. Different models are possible depending on the circumstances in each country.

Should clinical freedom be constrained in the name of self-sufficiency?

Clinical freedom should enable a physician to decide in a free and unbiased manner which is the most appropriate therapy to use for a particular patient. In order to implement the four aims of the German Haemophilia Society an average of 4-4.5 units of Factor VIII per capita of the general population per year is needed. At present European countries do not produce this amount, but to reduce the consumption of F VIII in therapy lowers treatment levels. Until plasma collection services in Europe can be expanded it is necessary that the additional, imported, sources of plasma are available, otherwise clinical freedom will be curtailed.

Economic issues in European self-sufficiency.

Future clinical practice in haemophilia care must make optimum use of resources and provide the highest quality products and services in an efficient and effective manner. Studies show that prophylactic therapy, compared with on-demand therapy, results in less time off work--that is, a smaller loss in productivity. However, prophylactic therapy requires a three- to five-fold greater annual amount of factor VIII than does on-demand therapy. Further study is needed to determine the optimum therapeutic strategy that gives the best cost v. benefit situation.

Do safety issues of plasma products constrain self-sufficiency?

The ultimate responsibility for selecting and administering plasma products to patients rests with the prescribing physician, and it is for him/her to choose the safest product available. However, liability for a product with a full licence rests exclusively with the licence holder. After the problems of HIV and hepatitis C the safety of plasma-derived products has become of paramount importance. Particularly in the public sector, financial, strategic and political obstacles may adversely influence the quantity, quality and safety of plasma collection. The safety of blood products can be substantially enhanced by the harmonization of technical standards across both public and private sectors, thus supporting EC Directive 89/381. Additionally, the goal of European rather than national self-sufficiency should be encouraged.

Is haemophilia prophylaxis achievable in the context of self-sufficiency?

In Sweden prophylactic treatment in haemophilia was introduced in 1958. Patients receiving prophylactic treatment have less time off school or work, require less hospitalization, have fewer joint bleeds, and generally lead as near normal life as possible. Although prophylaxis is expensive the cost is off-set by the improvement in quality of life and in productivity. At present, Sweden is almost self-sufficient in blood products for prophylactic treatment of haemophiliacs.

How will immune tolerance protocols affect self-sufficiency goals?

Inhibitor development is a serious complication in haemophilia, and its treatment, immune tolerance therapy, is an expensive part of haemophilia treatment. However, the therapy can lead to an increased lifespan and improved quality of life. If commenced sufficiently early in the disease, it can help to reduce the overall amount of factor VIII concentrate, or other plasma derived therapeutic agents required during life.

Will recent innovations in therapy save perceived deficiencies in self-sufficiency policies.

Future treatment for patients with haemophilia may include the use of either gene therapy, recombinant factor VIII, recombinant factor IX, or high-purity factor IX. Studies on gene therapy are still at the pre-clinical stage, while clinical trials of recombinant factor IX are expected to start by mid-1995. High-purity factor IX concentrates are available and are the treatment of choice for patients with haemophilia B in the absence of a source of recombinant factor IX. Recombinant factor VIII provides a renewable and unlimited source of factor VIII, and is a safe and effective treatment for haemophilia A.

The use of purified clotting factor concentrates in hemophilia. Influence of viral safety, cost, and supply on therapy.

Treatment of hemophilia, although greatly improved in recent years, continues to be problematic owing to infectious complications of blood product replacement therapy. This report examines the therapeutic options presently available for the treatment of hemophilia, focusing on the potential for repeated viral exposure to influence the progression of infectious disease, decreased risks of viral transmission with blood products produced using newer viral inactivation procedures, higher economic costs of newer blood products, and the current inadequate supply of blood products in the United States.