Desafíos en el empleo de los medicamentos huérfanos

Las enfermedades raras son aquellas que tienen baja prevalencia y que, por lo tanto, el desarrollo de medicamentos para tratarlas no es rentable para las empresas farmacéuticas debido a la baja demanda. A pesar de que ya se cuenta con diferentes políticas públicas alrededor del mundo para incentivar a las industrias farmacéuticas a investigar estos medicamentos, conocidos como medicamentos huérfanos, su desarrollo conlleva muchas dificultades en las evaluaciones clínicas y el precio final para el público es muy elevado. Si bien en años recientes se ha planteado el uso de tecnología de impresión en 3D para producir estos medicamentos o incluso recurrir a otros medicamentos previamente aprobados para tratar enfermedades raras, existe un historial de mal uso de las legislaciones por parte de las empresas con el fin de generar beneficios comerciales, por lo que estas políticas deben reforzarse para que cumplan su propósito; ayudar a una población muy vulnerable. El objetivo del presente texto es exponer los resultados de una revisión documental sobre el panorama científico y sociopolítico en el que se encuentra el problema de las enfermedades raras y los medicamentos huérfanos, así como las posibles soluciones que se están desplegando para abordarlo. Deriva de un estudio que se desarrolla en el momento actual en la Universidad Autónoma Metropolitana, de Ciudad de México.

The strange illnesses are those that have low prevalence and that, therefore, the development of medications to treat them is not profitable for the pharmaceutical companies due to the drop demands. Although it is already counted with different political public around the world to motivate to the pharmaceutical industries to investigate these medications, well-known as orphan medications, their development bears many difficulties in the clinical evaluations and the final price for the public it is very high. Although in recent years he/she has thought about the use of impression technology in 3D to produce these medications or even to appeal to other medications previously approved to treat strange illnesses, a record of wrong use of the legislations exists on the part of the companies with the purpose of generating commercial benefits, for what these politicians should be reinforced so that they complete its purpose; to help a very vulnerable population. The objective of the present text is to expose the results of a documental revision on the scientific and sociopolitical panorama in which is the problem of the strange illnesses and the orphan medications, as well as the possible solutions that they are spreading to approach it. It derives of a study that is developed in the current moment in the Metropolitan Autonomous University, of Mexico City.

Research advances in pharmacotherapy for rare diseases in children / 中国当代儿科杂志

There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.

Resistência a Antimicrobianos: a formulação da resposta no âmbito da saúde global / Antimicrobial Resistance: formulation of the response in the global health context

RESUMO A Resistência a Antimicrobianos (AMR) tem se revelado como um dos maiores problemas para a saúde pública no nível global. O objetivo deste artigo foi analisar a formulação da resposta à AMR negociada no âmbito da Organização Mundial da Saúde (OMS) por seus Estados-Membros. Foram analisados os relatórios e resoluções produzidos na Assembleia Mundial da Saúde no período de 1998 a 2019. Os achados indicam que, a partir de 2014, foram estabelecidas condições de possibilidade para a aprovação do Plano de Ação Global em AMR de forma mais robusta, abrangendo o conceito de Saúde Única e envolvendo outras instâncias internacionais (FAO, OIE, OMC e PNUMA). A análise dos conteúdos e o uso de diferentes referenciais analíticos, considerando dois setores econômicos - agropecuária e indústria farmacêutica -, mostraram-se relevantes para ilustrar a complexidade da temática, reforçando sua relevância global, reconhecendo a dimensão do uso de antibióticos em animais e as lacunas em inovação tecnológica. Como a OMS, além de ser um importante agente mobilizador para a resposta à AMR no nível global, tem garantido orçamento para ações nessa área mesmo em um contexto de desfinanciamento, conclui-se que a perspectiva da saúde pública deve prevalecer na resposta à AMR.

ABSTRACT Antimicrobial Resistance (AMR) has proved to be a major public health problem at the global level. This paper examined the formulation of the response to AMR negotiated through the World Health Organization (WHO) by its Member States. Related WHO reports and resolutions from 1998 to 2019 were analysed. The findings indicate that, from 2014 on, more robust conditions were established for approval of a Global Action Plan on AMR, encompassing the concept of One Health and involving other international entities (FAO, OIE, WTO and Unep). Content analysis and various analytical frameworks, considering two economic sectors (the livestock and pharmaceutical industries), proved relevant to illustrating the complexity of the issue, reinforcing its global importance and acknowledging the extent of antibiotic use in animals and the gaps in technological innovation. As the WHO is not only an important agent for mobilizing the response to AMR at the global level, but - despite a context of de-funding - has guaranteed a budget for action in this area, it is concluded that the public health perspective should prevail in the response to AMR.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health / O caso do eculizumabe: judicialização e compras pelo Ministério da Saúde

ABSTRACT OBJECTIVES This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

RESUMO OBJETIVOS O estudo examinou as aquisições de eculizumabe, um anticorpo monoclonal de alto custo utilizado no tratamento de doenças raras, pelos órgãos federais brasileiros, em termos das quantidades compradas, gastos e preços. MÉTODOS Foram analisadas compras de eculizumabe realizadas entre março de 2007 e dezembro de 2018, por meio de dados secundários extraídos do sistema de compras do governo federal (Siasg). Foram examinados o número de compras, quantidades adquiridas, número de doses diárias definidas por 1.000 habitantes por ano, gastos anuais e preços praticados. Os preços foram corrigidos pelo índice nacional de preços ao consumidor amplo para dezembro de 2018. Regressão linear foi utilizada para análises de tendência. RESULTADOS Todas as aquisições por órgãos federais foram realizadas pelo Ministério da Saúde. As compras se iniciaram em 2009, sendo efetuadas por dispensa de licitação e para atendimento de demanda judicial. Houve tendência crescente no número de compras e quantidades adquiridas ao longo do tempo. Foram realizadas 283 compras, totalizando 116.792 unidades adquiridas, 28,2% compradas em 2018. Os gastos totais contratados corrigidos somaram mais de R$ 2,44 bilhões. Após a aprovação do registro pela Agência Nacional de Vigilância Sanitária, o preço médio ponderado caiu aproximadamente 35%, para valores abaixo dos preços estabelecidos pela Câmara de Regulação do Mercado de Medicamentos. CONCLUSÃO O eculizumabe representou gastos extremamente significativos para o Ministério da Saúde no período. Todas as compras foram feitas para atendimento de demandas judiciais, fora do ambiente competitivo. Seu registro promoveu queda importante nos preços praticados. O estudo aponta a relevância do registro sanitário e da necessidade de monitoramento e auditoria permanentes das compras de medicamentos para atendimento de demandas judiciais.

The Enlightenment of Foreign Drug Security System for Rare Diseases to China / 中国药学杂志

OBJECTIVE: To explore the suggestions for the development of the medical security system and the medication for rare diseases (orphan drugs) in China and analyze the current progress of orphan drugs in China as well as other developed countries. METHODS: Based on literature search, the policies related with orphan drugs well as the medical security policies for patients with rare diseases in China and abroad were analyzed and summarized. RESULTS: Through analysis, it was found that the definition, regulation, and the research and development for orphan drugs started early in the developed countries and had made good progress. At the same time, they have relatively sound medical security system for rare diseases. At present,China has not established a complete policy, regulation and medical security system for rare disease, nor has an official definition of rare diseases. However, in recent years, China's policies on the research and approval of rare diseases and as well as medical serurity are improving day by day. CONCLUSION: Although China has not yet established a complete and perfect policy system for rare diseases, it has already made a series of policies according to our specific national conditions, which narrowed the gap between China and other developed countries. Our country should learn from foreign experience and consider the actual situation of our country, further complete the policies for rare diseases, and improve the diagnosis and treatment of patients with rare diseases.

Major routes for orphan drugs to be incorporated into the reimbursement system of UK and the enlightenment to China / 中国药科大学学报

@#In order to provide enlightening experience for the establishment of reasonable and diversified orphan drugs into the reimbursement system in China, the official websites of the National Institute for Health and Care Excellence(NICE)and the National Health Service(NHS)in the UK were inspected, collecting and summarizing the relevant documents, on the inclusion of orphan drugs into the reimbursement system. Relevant literatures were analyzed with theoretical studies on the accessibility of medicines for patients with rare diseases. In the NHS system, the inclusion of orphan drugs into the reimbursement system in the UK can be achieved mainly through seven routes, with three routes that are evaluated by NICE(MTA, STA and HST)and four are directly managed by the NHS(specialized commissioning, CDF, IFRs, CtE). Through the analysis of the inclusion of orphan drugs into the reimbursement system and the various problems in the UK, we have found some enlightening experience for the establishment of the reimbursement system for orphan drugs in China.

Progress in the diagnosis and treatment of rare diseases in the era of genomic medicine / 中华内分泌代谢杂志

There are many different kinds of rare diseases, of which most are with serious, complicated, and non-specific symptoms, and great difficulties exist in both diagnosis and treatment of rare diseases. In the era of genomic medicine, with the extensive application of next-generation sequencing technology and in-depth research of gene therapy, the diagnosis and treatment of rare diseases has ushered in a new turn. The next-generation sequencing technology enables high-throughput detection, assists in clinically efficient phenotypic assessment and disease diagnosis and promotes research on the pathogenesis and treatment of rare diseases; gene therapy technology continues to improve, and drugs are successively acquired, which brings the hope for cure to patients with rare diseases. This article will provide a brief overview of the advances and challenges of the diagnosis and treatment of rare diseases in the era of genomic medicine.

Progress in the diagnosis and treatment of rare diseases in the era of genomic medicine / 中华内分泌代谢杂志

There are many different kinds of rare diseases, of which most are with serious, complicated, and non-specific symptoms, and great difficulties exist in both diagnosis and treatment of rare diseases. In the era of genomic medicine, with the extensive application of next-generation sequencing technology and in-depth research of gene therapy, the diagnosis and treatment of rare diseases has ushered in a new turn. The next-generation sequencing technology enables high-throughput detection, assists in clinically efficient phenotypic assessment and disease diagnosis and promotes research on the pathogenesis and treatment of rare diseases;gene therapy technology continues to improve, and drugs are successively acquired, which brings the hope for cure to patients with rare diseases. This article will provide a brief overview of the advances and challenges of the diagnosis and treatment of rare diseases in the era of genomic medicine.

A incorporação do nusinersena no Sistema Único de Saúde: uma reflexão crítica sobre a institucionalização da avaliação de tecnologias em saúde no Brasil / The incorporation of nusinersen by the Brazilian Unified National Health System: critical thoughts on the institutionalization of health technology assessment in Brazil / La incorporación del nusinersén al Sistema Único de Salud: una reflexión crítica sobre la institucionalización de la evaluación de tecnologías en salud en Brasil

Resumo: Em abril de 2019, foi assinada a portaria de incorporação do medicamento nusinersena no Sistema Único de Saúde (SUS). É o medicamento mais caro já incorporado ao SUS, para uso no tratamento de atrofia muscular espinhal 5q tipo I. A incorporação é referida como um marco na tomada de decisão sobre novas tecnologias no SUS, a ser viabilizada por meio de acordo de partilha de risco. O trabalho discute o processo de incorporação do nusinersena, destacando aspectos contextuais, temporais e técnicos, além de possíveis consequências para a institucionalização da avaliação de tecnologias em saúde (ATS) no SUS. Seguiu método exploratório, com revisão de informações públicas produzidas pela Comissão de Incorporação de Tecnologias no SUS (CONITEC) e busca em bancos de dados governamentais de preços e compras. Foi produzida linha temporal descrevendo os pontos-chave do processo de incorporação. Houve dois pedidos de incorporação do medicamento. O primeiro, submetido pela Secretaria de Ciência, Tecnologia e Insumos Estratégicos (SCTIE) do Ministério da Saúde, negado por unanimidade, em novembro de 2018. Seguiu-se o pedido do Secretário da SCTIE à Advocacia-Geral da União (AGU), para que pudesse decidir de forma contrária à recomendação do plenário da CONITEC. A AGU recomendou uma nova submissão, feita pela empresa produtora e aprovada por unanimidade, em março de 2019. Não houve acréscimo de novas evidências ou redução de preço que justificassem a mudança de decisão. Não foram identificados os elementos constituintes do acordo de partilha de risco. São sinalizados problemas de transparência e accountability, bem como riscos ao processo de institucionalização da ATS que vinha em curso no SUS.

Abstract: In April 2019, a ruling was signed for the incorporation of the drug nusinersen by the Brazilian Unified National Health System (SUS). Nusinersen is the most expensive drug ever incorporated by the SUS and is used to treat type I 5q spinal muscular atrophy. The incorporation has been described as a milestone in decision-making on new technologies in the SUS, enabled through a risk-sharing agreement. The article discusses the process involved in the incorporation of nusinersen, highlighting the context, timing, and technical issues, in addition to possible consequences for the institutionalization of health technology assessment (HTA) in the SUS. The study used an exploratory method, reviewing public information produced by the Commission for Incorporation of Technologies in the SUS (CONITEC) and searches in government databanks on prices and purchases. A timeline was produced, describing the key points in the process of incorporation. There were two formal requests for the drug's incorporation. The first was submitted by the Division of Science, Technology, and Strategic Inputs (SCTIE) of the Brazilian Ministry of Health and was turned down unanimously in November 2018. This was followed by a petition by the head of the SCTIE to the Attorney General's Office (AGU) to overrule the recommendation by the CONITEC plenary. The AGU recommended a new submission, made by the drug's manufacturing company, which was approved unanimously in March 2019. The was no addition of new evidence or a price reduction to justify the change of decision. No elements were identified in the risk-sharing agreement. This suggests problems of transparency and accountability, as well as risks in the process of institutionalization of HTA that had been underway in the SUS.

Resumen: En abril de 2019, se firmó el decreto de incorporación del medicamento nusinersén en el Sistema Único de Salud brasileño (SUS). Es el medicamento más caro que se ha incorporado al SUS para su uso en el tratamiento de la atrofia muscular espinal 5q tipo I. La incorporación del mismo está considerada como un marco de referencia en la toma de decisiones sobre nuevas tecnologías en el SUS, que puede ser viable mediante el acuerdo de distribución de riesgo. El trabajo discute el proceso de incorporación del nusinersén, destacando aspectos contextuales, temporales y técnicos, además de posibles consecuencias para la institucionalización de la evaluación de tecnologías en salud (ETS) en el SUS. El trabajo siguió el método exploratorio, con una revisión de la información pública, generada por la Comisión de Incorporación de Tecnologías en el SUS (CONITEC) y la búsqueda en bancos de datos gubernamentales de precios y compras. Se creó una línea temporal, describiendo los puntos-clave del proceso de incorporación. Hubo dos peticiones de incorporación del medicamento. La primera, sometida a la Secretaría de Ciencia, Tecnología e Insumos Estratégicos (SCTIE) del Ministerio de Salud, rechazada por unanimidad, en noviembre de 2018. A lo que le siguió la petición del Secretario de la SCTIE a la Abogacía-General de la Unión (AGU), para que pudiese decidir en otro sentido respecto a la recomendación del pleno de la CONITEC. La AGU recomendó una nueva remisión, realizada por la empresa productora y aprobada por unanimidad, en marzo de 2019. No se produjo un incremento de nuevas evidencias o una reducción del precio que justificasen el cambio de decisión. No se identificaron los elementos constituyentes del acuerdo de distribución de riesgo. Se señalaron los problemas de transparencia y rendición de cuentas, así como riesgos para el proceso de institucionalización de la ETS que estaba en curso en el SUS.

Preliminary study on the global funding pattern of rare diseases / 国际药学研究杂志

Rare diseases are mostly chronic and serious diseases, which can cause multi-organ dysfunction, and generally lack effective drugs for treatment. Basic research on rare diseases and drug development of orphan drugs have received widespread attention worldwide. In 2018, ”China's First List of Rare Diseases”was officially released, and a to-tal of 121 diseases were included, achieving a historic breakthrough in the support of rare diseases and greatly promoting the development of researches on rare diseases in our country. However, China has not yet defined rare diseases, and there is no perfect research funding system for basic research on rare diseases. To this end, this paper compares the fund-ing structure of basic research projects for rare diseases in China and the world. In addition, drawing on the experience of global rare disease funding, we put forward the policy recommendations for the financing of rare diseases in China, in or-der to provide reference for the Chinese government to introduce research projects for the development of rare diseases, and to optimize the funding system.

Considerations on the feasibility of using retrospective database in the study of rare diseases / 国际药学研究杂志

Retrospective database is one of the data sources of real-world study, which has the advantages of abundant sample size, large amount of information and multi-dimension, and can support many types of quantitative re-search. On the one hand, rare diseases have the characteristics of low prevalence and the pathogenesis is unclear some-times. On the other hand, the lack of epidemiological investigation of rare diseases in China poses a challenge in the de-velopment and economic evaluation of rare disease drugs. This paper briefly describes the characteristics of the retrospec-tive database, and takes the health administrative data and electronic medical record as examples. Then, we discuss the feasibility of using such data to carry out epidemiological research and economic evaluation of rare diseases. Furthermore, we clarify some specific key points worth mentioning in advance in terms of study designs and protocols. Lastly, we pro-vide a reference for the subsequent use of retrospective data in conducting practical research.

Suggestions on the development of real world study on the rare diseases and orphan drugs / 国际药学研究杂志

Rare diseases and orphan drugs have always attracted great attention. Due to the low incidence and wide distribution of patients, it is difficult to diagnose the diseases and develop the therapeutic drugs. Countries around the world have put forward a number of decision-making policies to stimulate the research and development of orphan drugs. In recent years, the real world study(RWS)has been proposed as a new research method. Compared with the tradi-tional randomized controlled clinical trials(RCT), RWS is more conducive to the early detection and diagnosis of rare diseases and the clinical research and clinical reevaluation of orphan drugs. This paper reviews the current situation of real world data study on the use of drugs for rare diseases at home and abroad, and puts forward related suggestions for its development in China.

Plasma protein products for the treatment of rare diseases / 国际药学研究杂志

Plasma protein products are also called blood products. At present, more than 30 kinds of blood prod-ucts have been issued worldwide. Because of their particular source of raw materials as well as the safety, reliability and irreplaceability in the treatment of some diseases, many blood products are in short supply in the market. Rare diseases are usually caused by genetic deficiency, autoimmunity, allergy and so on, which imposes a huge burden on patients and their families. Orphan drugs generally include the products of diagnostic reagents, vaccines, medicines and medical devices used for the prevention, diagnosis and treatment of rare diseases and rare conditions. Since the adoption of the Orphan Drug Act(ODA)in the United States in 1983, many countries or regions have passed the relevant laws aiming to encourage enterprises to develop orphan drugs by means of the research funding, tax relief, priority approval and market monopoly. The pass of ODA has greatly promoted the development of related blood product enterprises. This paper sum-marizes the plasma protein products approved by the pharmaceutical regulatory departments of the United States, the Eu-ropean Union, Japan and Australia as orphans, including four categories and 18 varieties, accounting for 56% of all plas-ma protein products in the world. At present, China has not yet enacted legislation to define rare diseases and orphan drugs, which has restricted to a certain extent the development of domestic blood product enterprises. The policy divi-dends from ODA will help the development of domestic blood product enterprises and narrow the gap between the domes-tic enterprises and the international blood product giants.

Off-label drug use in the treatment of rare diseases:the current situation / 国际药学研究杂志

The diagnosis and treatment of rare diseases are a significant social public health work. Due to the low variety and poor accessibility of orphan drug, off-label use is common in the field of rare diseases at home and abroad. Off-label use may be the effective treatment for life-threatening diseases in patients with rare diseases, but it also raises issues related to drug safety and efficacy, medical liability and drug reimbursement, so the supervision of off-label drug use is of particular importance. This article reviews the current situation of off-label drug use and their application in thefield of rare diseases treatment, hoping to arouse widespread concern in society and ensure medication safety for patients with rare diseases through the joint efforts of medical institutions and regulatory agencies.

Suggestions for promoting domestic clinical trials of medicinal products for rare diseases / 国际药学研究杂志

Regardless of rare or common diseases, it is a common desire to shorten the time period of drug devel-opment. This is of particular importance for rare diseases because the most of rare diseases are lack of sufficient therapeu-tic methods. The incentive policy for the development of rare disease drugs(also called orphan drugs)was first adopted by the United States in the Orphan Drug Act in 1983, and correspondingly, most of clinical trials of the orphan drugs are seen in the United States. The clinical trials of orphan drugs are also increasingly on the rise in China. The main target diseases of the major portion of orphan drugs in clinical trials are mainly the rare cancers, and most of them are in the phaseⅡtrials. The clinical trial is a particular step in the orphan drug development. Besides the need of policy support, it still suffers from severe challenges in the clinical trial design and the clinical trial implementation, including the insuffi-ciency in the understanding of natural history and mechanism of the diseases, the impossibility to conduct the random-ized controlled clinical trial, the requirement for innovated design and more sensitive outcome measures to evaluate effi-cacy, the difficulty in enrolling patients to participate in the trials, and the ethical conflict. The solutions to these prob-lems will require the joint efforts of all parties involving the government, pharmaceutical companies, medical institu-tions, and patient organizations.

Considerations on the health techology assessment for rare diseases and orphan drugs in China / 国际药学研究杂志

There are about 7000 kinds of rare diseases in the world;the estimated number of patients with rare diseases is 4.3% of the world population and it is therefore a serious public health issue. For rare diseases, two questions are critical: (1)research and development for innovative treatments/medicines(orphan drugs);(2)access to launched orphan drugs in terms of availability and affordability. Many countries, including China, have paid significant attentions to the first question in terms of the regulatory review policy and financial incentive. As to the second question, there is a great difference in access to orphan drugs in different countries and regions due to many factors, including the different medical care systems and high drug expenses. Recently, health technology assessment(HTA)has played an important role in evaluating clinical and economic value of innovative medicines, including orphan drugs. This paper discusses how to do HTA evaluation on orphan drugs in China with several policy suggestions.

Consideration of pharmacoeconomic evaluation model and standard of payment threshold for rare diseases in China / 国际药学研究杂志

Rare diseases are usually defined as diseases with a low incidence in the population. According to re-ports, there were 6084 rare diseases found worldwide in 2016, involving 3715 related genes. 80% of rare diseases are caused by heredity, dominant or recessive inheritance or mutations. The definition of rare diseases by”incidence”in the population varies from country to country, like the EU <1/2000 and the United States <1/2500. A drug used to prevent, treat, or diagnose a rare disease is called an orphan drug. Due to the difficulty of research and development in this small target population, the high investment risk and the high R&D cost, the problem associated with high price of orphan drugs is very prominent. In the cost-effectiveness evaluation, the resulting incremental cost-effectiveness ratio(ICER)is likely to exceed the willingness to pay threshold adopted by most countries and regions, resulting in multiple countries raising its willingness to pay threshold reference standard(3-25 times GDP per capital)for orphan drugs, or simply ex-empting health technology assessment(HTA)assessment for orphan drugs and only evaluating the impact on medical in-surance fund. This paper systematically reviewed the various internationally accepted orphan drug HTA assessment meth-odologies. Based on the characteristics of rare diseases, the paper discusses the establishment of a model for the evalua-tion of orphan drugs and the multi-dimensional value assessment framework for HTA. At the same time, according to the internationally accepted norm, the paper also explores the way to determine the willingness to pay threshold in HTA as-sessment for orphan drugs in China.

Characteristics of drug policy and pharmacoeconomics study on rare diseases / 国际药学研究杂志

At present, we are facing challenges in the development of rare disease drugs. The paper introduces the ethical theories of rare disease treatment, the characteristics of pharmacoeconomic evaluation on orphan drugs, the risk of reimbursement in medical insurance funds, the international experiences on the balance between the accessibility and cost containment of high-cost orphan drugs, the orphan drug list promulgated by Hong Kong SAR of China in 2019 and the status quo of orphan drugs in China. The author also analyzes the international practice from different perspec-tives, such as, the Orphan Drug Act(ODA)in the United States, the new concept of high specific technology introduced by National Institute Health and Clinical Excellence(NICE)in the UK, the retrospective review of pharmacoeconomics of orphan drugs by National Centre for Pharmacoeconomics(NCPE)in Ireland, the principles of orphan drug evaluation by TLV in Sweden, a special research program on the cost of orphan drugs in Turkey, and the four measures to control the cost of high-priced drugs in the Republic of Korea. The aim of this paper is to introduce international experiences for reference on the formulation of drug policies in rare diseases and development of related pharmacoeconomics in China.

Analysis on the Medical Insurance Policy and Medical Insurance Catalog for Rare Diseases in China / 中国卫生经济

Objective:To explore the status quo and development suggestions of the availability of medical insurance for orphan drugs in China through the analysis of international,national and local rare disease drug use system and policy,and the species of orphan drugs in China's health insurance directory.Methods:The website of local government and the Chinese database were retrieved by computer,and the relevant policies and regulations of rare diseases and orphan drugs were obtained.The information of rare diseases and orphan drugs in National Basic Medical Insurance,Employment Injury Insurance and Maternity Insurance Drug Catalog was systematically extracted.Results:There was no official definition of rare diseases and the official list of rare diseases in China.In recent years,with regard to the approval policy and measures of rare diseases and the R&D(research and development) of orphan drugs fully developed.In the medical security,many provinces and municipalities introduced the popular characteristics of local rare diseases and the implementation of the rare diseases protection policy,however,the whole policy of nation level was still blank.The edition of 2017 of the basic medical insurance,industrial injury insurance and maternity insurance drugs directory contained 53 kinds of orphan drugs,added 7 kinds compared to the version of 2009 version,an increase of 15.22％.17 kinds of rare diseases were covered,involving blood diseases,bone or cartilage diseases,congenital metabolic disorders,brain or nervous system diseases,immune system diseases,skin diseases,digestive systemn diseases,endocrine system diseases and other treatment fields.Compared with previous years,the new version of the medicare drug list of orphan drugs also increased the dosage form,of which class A had more types of formulations rather than class B.Conclusion:China's rare disease social security system policy focused on the field of R&D approval,medical security was dominated by local policy-based.The scope of orphan drugs in the new edition of national health insurance drug list was expanded,but the supporting policies needed to be improved.Therefore,the problem of rare disease social security system policy in China needed to be paid more attention.

Comparative Study and Enlightenment of the R&D Incentive Policies for Orphan Drugs in USA and the EU / 中国药房

OBJECTIVE:To provide references and suggestions for building and improving the R&D incentive policies for or-phan drugs in China. METHODS:The R&D incentive policies for orphan drugs in USA and the EU were compared in aspects of its legislative history,incentive measures and effects. And suggestions for improving related policies in China were put forward. RE-SULTS & CONCLUSIONS:The R&D incentive policies for orphan drugs in USA and the EU respectively started from Orphan Drug Act in USA(1983)and Orphan Drug Management Specification in the EU(1999),then formed relatively complete system by continuous improvement. The USA and the EU showed differences in its certification standard,procedure and specific incentives [R&D funding,tax deduction,fee reduction,additional incentives for micro and small and medium enterprises (SMEs),market exclusivity and special approval procedure],etc. In terms of fee reduction,for example,prescription application fee,production cost and drug confirmation fee were exempted in USA,while arrangement assist fee,initial and follow-up fee,checking fee before approval,initial listing type were reduced to a certain percentage in the EU. After developing incentive policies for orphan drugs, there is great increase in numbers of recognized qualifications and listing,SMEs have become new force in orphan drug R&D, R&D investment covers all types of diseases,orphan drug R&D are becoming the main direction of drug innovation and biotechnol-ogy development. China should determine the relevant legislation of R&D incentives for orphan drugs as soon as possible,set certi-fication and improve specific measures of R&D incentives for orphan drugs from multiple aspects,while strengthen the cooperation with other countries in qualification and R&D incentives.