【作者】 龚时薇；

【导师】 张亮；

【作者基本信息】 华中科技大学 ， 社会医学与卫生事业管理， 2008， 博士

【摘要】 研究目的:近年来我国出现了一系列罕见病患者无药可治或用药短缺的情况,罕见病患者的用药状况不容乐观,生命健康受到严重威胁。为改善我国罕见病患者的用药状况,本研究从促进我国罕见病患者用药可及性视角,对我国罕见病患者药品可及性状况、国际罕见病药品制度体系构成与我国罕见病药品制度建设环境进行系统的分析,以期为我国罕见病药品制度的建设提供一些政策决策依据。研究方法:依据研究内容需要整体采取文献研究与实证研究方法。其中,文献研究应用描述性研究法、比较分析法;实证研究包括现存统计数据分析法、典型案例分析法和专家访谈法。主要研究结果:1.罕见病与罕见病药品的概念与性质罕见病WHO定义为发病率在0.65‰～1‰之间的疾病或病征。目前WHO已确认的罕见病约5000～6000种,约占人类疾病的10%。罕见病中约80%为遗传性疾病,90%为严重性疾病。尽管单一罕见病的发病率低,受累人群少,但整体罕见病受累人群相当大,欧美总计的受累人群大约有5000～6000多万人。目前,大部分的罕见疾病没有恰当的药物治疗。罕见病药品简称为罕用药,是以罕见病为目标,用于治疗、预防、诊断这类疾病且商业投资价值低的药品。罕用药由于市场容量小,商业利润低,在市场经济的条件下,医药企业自愿投资罕用药研发、生产与供应的可能性几乎为零。罕用药低流量、低商业价值与高成本,使得卫生事业的公益性与医药微观组织的经济性之间存在严重的冲突。因此,在市场经济条件下,要促进患者罕用药的可及性,政府干预必不可少。2.罕见病药品可及性的概念与评价指标我们创新性地将药品可及性的含义界定为系统促进药品从物质状态转化为健康价值的过程。这一实现药品健康价值的过程包括了三个环节:拥有治疗药品(药品从无到有的可获得性过程)、可及治疗药品、合理使用治疗药品。由于罕见病患者的健康需要与罕见病药品的有效供给之间存在严重的缺口,所以,对于罕见病药品可及性的含义在这里更强调医药卫生系统能满足人们用药需要的保障能力,尚不涉及系统保证药品质量能力与药品被合理利用的程度。从患者可及药品的过程出发,结合国内外对药品可及性和医疗卫生可及性影响因素与评价指标研究成果,得出影响罕见病药品可及性的5个关键指标:可获得性、可利用性、可供应性、可负担性和系统反应性。3.我国罕见病患者药品可获得性状况1983-2007.12年间美国上市的针对315种罕见病征的罕用药约有254个,其中约有130个罕用药在我国上市,占美国获准上市罕用药总数的51.18%(130/254)。美国、日本、欧盟上市前八位疾病系统的罕用药共涉及95种罕见病、178种罕用药,我国上市85个,占47.75%(85/178)。4.我国罕见病药品研究项目分布情况1999-2007年度国家自然科学基金资助32种罕见病征366个基础研究项目,共计8935.8万元,其中药物研究项目63项,共计1487万元,占总金额的16.7%;在投入疾病类型上,消化系统和代谢系统罕见病、罕用药的基础研究投入上相对较低,分别占项目总数的0.27%、0.82%;血液和造血系统罕见病的基础研究投入相对较高,占项目总数的66.12%,投入经费占项目总经费的69.41%;在国家863计划、973计划资助项目中涉及罕见病、罕用药内容共7项;国家科技型中小企业技术创新基金项目共资助我国的中小型生物医药企业开展罕用药创新项目15项。目前,我国罕见病药品研发投入以政府投入为主,但是投入分布零散,没有总体布局与步骤,投入金额少,投入产出绩效不明显。5.我国罕见病患者用药可及性障碍分析(1)罕见病患者罕用药的可利用障碍:罕见病临床上不易确诊,无法得到恰当药物治疗,或用药存在风险;疾病确诊但无药可治或有药治疗但专利新药昂贵、老药易出现生产性或区域性短缺;医疗专家或区域性专业医疗服务机构,获得有效治疗药物的信息匮乏。(2)罕用药的生产、流通和使用阶段的供应障碍:供应来源相对单一,医药产业组织缺乏利润动机,医生缺乏标准的诊疗知识与信息,无法提供有效药品供应。(3)罕见病患者罕用药的可负担状况:诊疗周期长,缺乏医疗保险,疾病经济负担沉重。(4)影响医药卫生系统及时供应罕用药反应能力的障碍因素:没有罕见病与罕用药的明确界定,没有颁布罕用药国家药品目录、临床用药指南或药师手册,系统内从业者对罕见病与罕用药缺乏统一认识,患者及时获得有效替代治疗药物的机会低;在宏观与微观上都没有建立罕见病与罕用药的信息平台;缺乏药品短缺供应的宏观协调机制;医务工作者普遍缺乏罕见病诊疗技能与罕用药正确使用的专项培训,医院采购药品存在流通渠道限制等问题。6.国际促进患者罕用药可及性的管理制度体系的构成是一种以产业激励政策为导向的促进患者罕用药可及性的公共卫生政策。但要解决罕用药可及性问题,不仅是一部罕用药倾斜政策的作用,而是与国家的医学科学、生物技术、新药研发的激励制度、医药企业风险投资制度、药品短缺供应制度、医疗保险制度、罕见病信息管理制度、医务工作者的在职培训计划等全方位的制度设计相互配合共同作用的结果。研究结论:要改善我国罕见病患者的用药现状,我们需要从以下10方面入手:(1)国家应提高重视程度,明确政府责任。(2)明确罕见病与罕用药的界定。(3)建立罕见病与罕用药信息管理系统。(4)建立从罕用药研发到生产、流通、使用管理全过程的激励机制。(5)建立以医院为主导的罕用药协议供应模式。(6)提高基层医疗机构与社区卫生服务中心罕见病诊疗水平。(7)加强罕见病与罕用药的健康教育。(8)完善医疗保险制度,设立罕用药药品报销目录,提高患者用药的可负担性。(9)在国家药品储备中增设罕用药储备。(10)建立我国罕用药的技术审评机构,积极参与国际合作。创新点:(1)首次在我国以药品可及性视角研究罕见病药品的管理,首次引入系统反应性作为罕见病药品的可及性指标。(2)创建了八大疾病系统95种罕见病178个罕用药的国内与国际信息资源库,这是我国罕用药制度建设的基础。(3)采用一些新的思路研究罕用药制度。从药品可及性视角出发,发现国际罕用药制度所产生的社会经济价值,不仅是一部罕用药倾斜政策的作用,而是一个以可及性为目标的制度系统的结果。首次引入利益集团理论、机制设计理论解释国际罕见病药品制度体系;结合发达国家与一些发展中国家的经验,提出一些符合我国国情的制度建设建议,诸如企业低息贷款政策、公私合作模式、指定国家罕见病的医疗服务中心、重视基层与社区卫生服务中心罕见病诊疗水平建设、以医院为主导的罕用药协议供应模式、药品生产企业罕用药批准文号储备制度等措施。更多还原

【Abstract】 Aim:In recent years, increasing reports concerning shortage of drugs for rare disease treatment have been seen in all kinds of media. The drug accessibility of rare disease patients is not satisfying. Their health can not be assured. The present study analyzed the current medication status of rare disease patient in China, the international orphan drug management system and the orphan drug policy construction environment, aiming to improve the medication accessibility of Chinese rare disease patients.Methods:Literature and evidence-based studies were conducted based on need. In literature-based study, description study and comparative analysis were used; in evidence-based study, existing statistics analysis, classic-case analysis, expert interview were used.Main results:1. Definition of rare disease and orphan drug According to WHO, rare disease refers to those the incidence is with 0.65‰～1‰. So far, there are 5000～6000 kinds of rare disease reported, accounting for 10% of all human diseases. Among which, 80% are genetic diseases, 90% are critical diseases. although the incidence of a certain rare disease is low, but the total population affected is huge. The total affected population is around 50～60 million. Currently, most of the rare disease patients didn’t receive proper treatment. Orphan drugs are those intended to diagnose, prevent or treat rare diseases or pathologies that are serious or life threatening, and whose development costs are superior to the expected return on investment. Due to the low marketing and low profit and high cost, there is almost no drug company would like to invest on the R&D, production and supply. It is very necessary for the government to intervene to improve the accessibility of orphan drugs.2. Definition of accessibility of drugs for rare diseases we define the accessibility as the process of systemically transfer the drug from substance form to health value. This includes three steps: drug existence, drug availability, and the rpoper usage of the drugs. Five key factors were proposed to affect the accessibility of orphan drugs: availability, utility, deliverability, affordability and systemic reactivity.3. The current availability of orphan drug in China During 1983-2007.12, there are 254 orphan drugs for 315 rare diseases, among which, 130 were available in China, accounting for 51.18%. The orphan drugs for the top 8 systems involves 95 rare diseases and 178 orphan drugs in America, Japan and Europion Union. Among which, 85 were marketed in China, accounting for 47.75%.4. The research funding for rare disease in China During 1999-2007, there are 366 grants were funded by national natural science foundation of China for rare disease research, accounting for 89,358 thousand RMB. Among which, 63 grants were for drug research, accoungting for 14,870 thousand RMB and 16.7% in percentile. The rare diseases of digestive and metabolic system were funded relative lower, accounting for only 0.27%, 0.82% respectively. The rare diseases of hematopoietic system were funded relative higher, accounting for 66.12% in grant number and 69.41% in funding. There are seven“863”or“973”grants involving rare disease research. 15 grants were funded to pharmaceutical company to conduct orphan drug research. So far, the funding for orphan drug R&D is mainly form government and lack of systemic planning. The funding is too few and effect is not satisfying.5. Analysis of the factors affecting the accessibility of the medication of rare disease(1) utility disorder: not easy to diagnose; no proper drugs to use; too expensive; lack of proper information for rare disease;(2) production, supply and usage disorder; lack of profit motivation; lack of standard knowledge for rare disease;(3) affordability: long treating circle; lack of health insurance; high economic burden;(4) systemic reactivity disorder: no information platform for rare disease and orphan drugs; no standard training program for rare diseases;6. The analysis of foreign policies to improve orphan drug accessibility Industry motivation-Oriented public health policy. Combination of medical science, biotechnology, motivation of new drug R&D, risk investment policy, shortage-supply protocol, health insurance, rare disease information protocol, doctor training program.Conclusions: to improve the health status of rare disease patients, the following 10 aspects is noticed,(1) strengthen the government’s responsibility on rare diseases;(2) clarify the definition of rare disease and orphan drug in china;(3) establish the information system for rare disease and orphan drug in China;(4) establish the stimulating mechanism for the R&D, production, supply and use of orphan drugs;(5) establish the hospital-oriented supply contract for orphan drugs;(6) improve the diagnosis and treatment level for rare disease;(7) strengthen the health education about rare disease and orphan drug; (8) improve the health insurance protocol concerning rare diseases;(9) increase orphan drug preservation;(10) establish the orphan drug review system and seek more international cooperation.Innovation of research(1) Study orphan drug management from patient drug access view,introducing health system reaction indicator firstly;(2) Setting up an orphan drugs supply international information data for 178 orphan drugs of eight disease types;(3) Some new ideas on solving orphan drug access.Such as drug access-Oriented policy system,reasons analysis of orphan drug policy from Interest Groups Theory and Mechanism Design Theory , pharmaceutical industry low interest loan policy, Public-Private Partnerships Financing Pattern,advising clinical service centres for rare diseases,promoting community health effective intervention level for rare disease, hospital-based orphan drugs supply protocol, reserving orphan drug approval number regulation for pharmaceutical company .更多还原