Analysing criteria for price and reimbursement of orphan drugs in Spain.

OBJECTIVE: There are differences between countries regarding data requirements for orphan drug evaluation and it  is also unknown which criteria might determine the price and reimbursement decision. This study aimed to identify the key  criteria for price and reimbursement of orphan drugs in Spain, approved by the European Commission, between January 2012 and June 2018. METHOD: A descriptive analysis of the orphan drugs and its characteristics was performed. Outcomes criteria assessed  were: therapeutic area, existence of alternative treatment, rarity of the disease, clinical trial outcomes and therapeutic  positioning report assessment. Hypotheses for each variable regarding Spanish pricing and reimbursement were made  and tested with two regression analyses. RESULTS: Out of 78 orphan drugs approved by the European Commission, 82.1% asked pricing and reimbursement in  Spain. From this, 43.8% had pricing and reimbursement approved and 20.3% rejected. Mean time from Spanish  marketing authorisation approval to pricing and reimbursement approval was 12.1 ± 5.1 months. Having a positive  therapeutic positioning report and no therapeutic alternatives would be associated with a positive pricing and  reimbursement in Spain. CONCLUSIONS: It remains challenging to establish which are the driving criteria for pricing and reimbursement approval  of orphan drugs in Spain. Further research should be done including other variables that might influence the pricing and  reimbursement final decision in Spain.

Objetivo: Los requisitos para la evaluación de los medicamentos huérfanos difieren entre los países  miembros de la Unión Europea y tampoco se sabe qué criterios influyen en la decisión final sobre  precio y financiación. Este estudio ha tenido como objetivo identificar los criterios clave para establecer el precio y la financiación de los medicamentos huérfanos en España, una vez  aprobados por la Comisión Europea, entre enero de 2012 hasta junio de 2018.Método: Se realizó un análisis descriptivo de los medicamentos huérfanos y sus características. Los  criterios evaluados fueron: área terapéutica, existencia de tratamientos alternativos, rareza de la  enfermedad, tipo de resultados de los ensayos clínicos e informe de posicionamiento terapéutico. Para  cada variable se estableció una hipótesis con respecto a la aprobación de precio y  financiación y se analizaron con dos análisis de regresión.Resultados: De las 78 aprobaciones de medicamentos huérfanos realizadas por la Comisión Europea,  el 82,1% solicitaron precio y financiación en España. De estas, el 43,8% fueron aprobadas  y el 20,3% fueron rechazadas. El tiempo medio desde la aprobación de la autorización de comercialización en España hasta la aprobación del precio y la financiación fue de 12,1 ± 5,1  meses. Un informe de posicionamiento positivo y la falta de alternativas terapéuticas se asociaría con  una aprobación de precio y financiación.Conclusiones: Sigue siendo un reto establecer cuáles son los criterios clave para la aprobación de los  medicamentos huérfanos en España. Los próximos estudios deberían incluir un mayor número de  variables que puedan influir en el precio y la decisión de financiación.

Disease and economic burden for rare diseases in Taiwan: A longitudinal study using Taiwan's National Health Insurance Research Database.

BACKGROUND: High-cost orphan drugs are becoming increasingly available to treat rare diseases that affect a relatively small population. Little attention has been given to the prevalence of rare diseases and their health-related economic burden in Taiwan. OBJECTIVES: This study examined the national trends in the prevalence of rare diseases and their health-related economic burden (including medication costs) in Taiwan. METHODS: Rare disease-related claims data from 2003-2014 (12 years) from the National Health Insurance Research Database were used in this study. We used a time series analysis to assess trends in the yearly rates of treated patients with rare diseases, overall healthcare use, and expenditures, including drugs. RESULTS: During the 12-year study period, the estimated prevalence of rare diseases increased from 10.57 to 33.21 per 100,000 population, an average rate of a 19.46% increase per year. Total health expenditures for treatment of rare diseases increased from US$18.65 million to US$137.44 million between 2003 and 2014, accounting for 0.68% of the total national health expenditures in 2014. Drug expenditures for treatment of rare diseases increased from US$13.24 million to US$121.98 million between 2003 and 2014, which accounted for 71.00% and 88.75% of the health expenditures for patients with rare diseases in 2003 and 2014, respectively. In 2014, we found a 20.43-fold difference in average health expenditures and a 69.46-fold difference in average drug expenditures between patients with rare diseases and the overall population. CONCLUSIONS: The prevalence of rare diseases and the related economic burden have grown substantially in Taiwan over the past 12 years, and these trends are likely to continue. Drug expenditures accounted for almost 90% of health expenditures for rare diseases. Further analyses are underway to examine the economic burden of individual rare diseases.

New Therapeutic Uses for Existing Drugs.

Eighty percent of drugs that enter human clinical testing are never approved for use. This means that for every five drugs that make it into the clinic, there are four that failed to show effectiveness for treating the disease or condition the drug was designed to treat.This high failure rate means there are many existing, partially developed therapeutic candidates with known pharmacology, formulation, and potential toxicity. Finding new uses for existing experimental drugs or biologics "repositioning" builds upon previous research and development efforts, so new candidate therapies can be advanced to clinical trials for a new use more quickly than starting from scratch.Federal funding initiatives in the U.S. and UK started to support pre-clinical /or early stage trials for repositioning existing experimental drugs or biologics (therapies). This chapter covers some of the process issues that have been solved and the remaining challenges that are still in need of solutions. The chapter is primarily written from a U.S. federal funding perspective. The general concepts could be applied more globally to benefit rare and neglected disease populations. The drug development and process bottlenecks are the same for both rare and common disease.

Health Systems Sustainability and Rare Diseases.

The paper is addressing aspects of health system sustainability for rare diseases in relation to the current economic crisis and equity concerns. It takes into account the results of the narrative review carried out in the framework of the Joint Action for Rare Diseases (Joint RD-Action) "Promoting Implementation of Recommendations on Policy, Information and Data for Rare Diseases", that identified networks as key factors for health systems sustainability for rare diseases. The legal framework of European Reference Networks and their added value is also presented. Networks play a relevant role for health systems sustainability, since they are based upon, pay special attention to and can intervene on health systems knowledge development, partnership, organizational structure, resources, leadership and governance. Moreover, sustainability of health systems can not be separated from the analysis of the context and the action on it, including fiscal equity. As a result of the financial crisis of 2008, cuts of public health-care budgets jeopardized health equity, since the least wealthy suffered from the greatest health effects. Moreover, austerity policies affected economic growth much more adversely than previously believed. Therefore, reducing public health expenditure not only is going to jeopardise citizens' health, but also to hamper fair and sustainable development.

Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

BACKGROUND: The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. METHODS: Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. RESULTS: Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. CONCLUSION: The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.

High quality, patient centred and coordinated care for Alstrom syndrome: a model of care for an ultra-rare disease.

BACKGROUND: Patients with rare and ultra-rare diseases make heavy demands on the resources of both health and social services, but these resources are often used inefficiently due to delays in diagnosis, poor and fragmented care. We analysed the national service for an ultra-rare disease, Alstrom syndrome, and compared the outcome and cost of the service to the standard care. METHODS: Between the 9th and 26th of March 2014 we undertook a cross-sectional study of the UK Alstrom syndrome patients and their carers. We developed a semi-structured questionnaire to assess our rare patient need, quality of care and costs incurred to patients and their careers. In the UK all Alstrom syndrome patients are seen in two centres, based in Birmingham, and we systematically evaluated the national service and compared the quality and cost of care with patients' previous standard of care. RESULTS: One quarter of genetically confirmed Alstrom syndrome UK patients were enrolled in this study. Patients that have access to a highly specialised clinical service reported that their care is well organised, personalised, holistic, and that they have a say in their care. All patients reported high level of satisfaction in their care. Patient treatment compliance and clinic attendance was better in multidisciplinary clinic than the usual standard of NHS care. Following a variable costing approach based on personnel and consumables' cost, our valuation of the clinics was just under £700/patient/annum compared to the standard care of £960/patient/annum. Real savings, however, came in terms of patients' quality of life. Furthermore there was found to have been a significant reduction in frequency of clinic visits and ordering of investigations since the establishment of the national service. CONCLUSIONS: Our study has shown that organised, multidisciplinary "one stop" clinics are patient centred and individually tailored to the patient need with a better outcome and comparable cost compared with the current standard of care for rare disease. Our proposed care model can be adapted to several other rare and ultra-rare diseases.

Economic aspects of rare diseases.

Economic problems related to the prevention, diagnosis and treatment of rare diseases are presented paying particular attention to the costs of financing treatment, including the issue of its refund, which is a fundamental and difficult to solve economic problem of the health care system. Rare diseases, despite the low frequency of occurrence, together cover a large group of diseases being a serious medical, social and economic problem. The adoption of Polish National Plan for Rare Diseases resulting from the recommendations of the Council of the European Union, the extension of institutional activities related to the area of public health and social initiatives seeking innovative solutions to create a model of social support for patients and their families, with very high complexity of the issues regarding rare diseases, results in the need for a coherent, comprehensive, system operations and adoption of comprehensive solutions.

Creating a European Union framework for actions in the field of rare diseases.

Rare diseases, including those of genetic origin, are defined by the European Union as life-threatening or chronically debilitating diseases which are of such low prevalence (less than 5 per 10,000). The specificities of rare diseases - limited number of patients and scarcity of relevant knowledge and expertise - single them out as a unique domain of very high European added-value. The legal instruments at the disposal of the European Union, in terms of the Article 152 of the Treaties of the European Union, are very limited. However a combination of instruments using the research and the pharmaceutical legal basis and an intensive and creative use of funding from the First Public Health Programme 2003-2008 and from the Second Health Programme 2008-2013 has permitted to create a solid basis that Member States have considered enough to put rare diseases in a privileged position in the health agenda. The adoption of the Commission Communication, in November 2008, and of the Council Recommendation, in June 2009, and the future adoption of the Directive on Cross-border healthcare, maybe during 2010, have created an operational framework to act in the field of rare disease with European coordination in several areas (classification and codification, European Reference Networks, orphan drugs, European Committee of Experts, etc.). In conclusion, Rare diseases is an area with enormous and practical potentialities for the European cooperation.