【作者】 黄登笑；

【导师】 黄淇敏；

【作者基本信息】 上海交通大学 ， 企业管理， 2011， 博士

【摘要】 人类应用药品治疗疾病已有几千年的历史,作为防病治病的重要武器,药品对于保障人类身体健康和促进社会文明发展起着不可忽视的作用。但在使用过程中,在发挥药品防病治病功能的同时,也伴随出现了与用药目的无关甚至相反的有害作用。上个世纪的反应停、磺胺酏等事件,敲响了人类对药品不良反应进行防范的警钟。近年来国内发生的龙胆泻肝丸、葛根素注射剂、鱼腥草注射剂等不良反应事件,进一步表明药品具“双刃剑”的特性,即在有治疗作用的同时,也会发生与治疗目的无关的或者是出乎预料的有害反应。现实生活中日益增多的药品不良反应损害事件、药品不良反应纠纷和药品不良反应诉讼,使药品的安全合理使用陷入了困境。在国外,自1957德国年沙利度胺事件发生后,德国、美国、日本、瑞典、我国台湾地区等针对药品不良反应造成的损害,逐渐建立了相应的ADR补偿救助制度。而在国内,随着药品不良反应事件的增多,虽然补偿制度方面仍然未提上日程,但在借鉴国外经验的基础上,1988年开始开展药品不良反应监测报告试点工作;1989年组建成立了卫生部药品不良反应监察中心;1998年3月正式加入WHO国际药品监测合作中心;1999年11月,《药品不良反应监测管理办法(试行)》颁布,2001年建立并实施了药品不良反应信息通报制度,2002年全国31个省市全部建立了药品不良反应监测中心;2003年3月,《药品不良反应报告和监测办法》正式实施。现阶段,逐渐形成国家到地方的ADR监测和报告网络体系。对于药品不良反应补偿制度的建设上,国内一些学者在参考国外现有制度的基础上,呼吁建立相应的补偿制度。鉴于此,本文从建立药品不良反应补偿制度入手,分析比较了国内外药品不良反应补偿制度的要素,然后对各要素进行深入分析研究,同时利用AHP方法、支付意愿法(WTP)、多元线性回归分析等对药品不良反应补偿体系中各个要素进行实证分析,以期为政府在建立药品不良反应补偿制度中的政策和操作中提供选择。本研究循着要建立药品不良反应补偿体系这一目标,首先,应用比较法、归纳法和演绎法,对国内外现行制度及相关技术环节进行分析。研究发现,在我国属大陆法系的国家,行政权力比较集中,要使药品不良反应制度建立,需要有明确而专用的法律支持,才有可能在法律规定的基础上设置为药品不良反应受损害者提供补偿,然后才能考虑补偿资金的来源、资金的管理、药品与受损之间的因果关系、受损程度的认定、补偿的标准等。而从国内目前来看,因为没有专门的药品损害补偿法律,造成因为药品不良反应受害者无法合理得到补偿,同时,造成国内学者对于这一领域的研究也处于文献比较研究阶段。本文通过系统的分析比较,提出了在建立药品不良反应补偿制度过程中需要考虑的关键要素,为进一步研究打下一个坚实基础。其次,利用层次分析法与综合指数法,将目标问题分解成各种组成要素,并按要素间的相互关系将要素层次化,形成一个递阶层次结构模型,然后按层分析,两两比较,最终获得最低层因素对于最高层(目标层)的权重,再通过综合指数法的演算,得到一个因果判断量化的指数标准,这就把定性的描述转换为定量的分析。在计算模型建立后,如果需要判断个体受损情况与药品之间的因果关系,将个体的涉及因素纳入模型进行计算,根据得到的结果,就可判断个体受损害情况与药品之间存在的因果关联程度的大小,从而使得判断过程简单而易用。同时,运用实证方法对其进行验证,结果具有很好的一致性。第三、以意愿调查为理论依据,利用非参数检验、多元logistic回归分析法。结果发现,相关方均在不同损害级别间均做出选择某一级损害作为补偿起点,这反映出相关方认为补偿不是全部的,而是对部受损害者补偿。同时,相关方选择起点级别高低不一,又反映相关方对于受损害者补偿范围认识不统一。经统计检验发现,政府认为设置起付级别应该高一些;药品生产企业次之;而药品经营与使用机构认为起付级别门槛应该低一些,这样有更多的受损者可以纳入补偿范围。对于补偿额的确定,相关方认为损害程度比5级轻时,相关方补偿意愿低;而损害在4级至3级之间有明显拐点,相关方的赔付意愿发生明显变化,同时愿意支付的经济补偿额明显上升。损害重于3级以上时,损害级别与补偿金额显线性变化。对于死亡情况,相关方认为应获得最低30万元以上补偿。对于损害责任的承担方式,研究发现药品生产企业与政府部门应承担最主要的责任,而药品经营与使用单位承担次要责任,受损害人不承担责任。从筹资水平来看,相关方认为需要建立多层次、多渠道的筹资模式,任何独立一方单独承担赔付的金额都是难以为继的。对政府责任的分析发现,相关方均一致认为政府应该承担相应的责任,不能将政府排除在制度建立之外,如药品生产企业希望政府以按比例出资的方式来承担,而政府原来只希望在建立政府时出一部分引导资金,说明相关方各自定位存在一定差异。通过多元logistic回归模型对各级补偿影响因素的分析发现,可以发现对不同级别损害回归时,其影响因素不一样,在七级损害时,当a=0.05时,其模型中影响因素不同;对各个模型因素进行数量比较,损害在7级至1级之间,随着损害程度加深,各个模型中影响因素在减少,这说明如果建立补偿制度,生产企业仍然有意愿进行筹资补偿。第四、ADR伤害程度的分级,是构建药品不良反应补偿体系的基础,是必需界定的因素,一方面有助于整个救助体系的建立,另一方面在赔付过程中起到赔付标准的作用。研究中结果发现,运用数理统计学的一些方法与指标,以WHO器官与系统分类为基础,损害程度以6级分类来描述,通过专家评分,经统计处理后,得到一个量化的初步药品不良反应损害分级判断表。第五、筹资到的资金如何管理?这也是建立药品不良反应补偿制度必需考虑的一个问题。研究中以委托-代理理论为基础,通过分析得出,在委托人可以监督代理人活动时,代理人努力(或偷懒)工作时的收益一定要高于其机会成本收益,否则代理人将不接受代理,政府只能选择内部分;在委托人不能监督代理人活动时,代理人努力(或偷懒)工作时的收益一定要高于其机会成本收益,否则代理人将不接受代理,政府只能选择内部分;当选择一个努力p(或偷懒q),付出成本足够大而又没有相当的收入来保证,努力代理人一旦发现自己无利可图,自然会放弃对投资经营的积极性,因此代理人是否选择接受代理,仍然根据自己的收益来做出判断。在代理人只有一项工作时,代理人选择将会有自身利益的而进行考虑。最后,本文探讨了我国建立药品不良反应补偿体系及其相关要素的理论作用,并提出了相关的政策建议。本文的创新点主要体现在以下三个方面:一、以系统论观点为指导,对药品不良反应补偿体系及各组成要素从多学科角度进行较为全面的、系统的深入研究,这在我国同类研究中还不多见,从而弥补了当前国内对药品不良反应补偿研究分散的状况。二、通过数理统计构建了药品不良反应因果关系判断与药品不良反应损害程度分级二个核心要素的量化标准,在判断标准上从以往定性判断改变为以定量判断为主的方法,弥补了国内外研究在这方面的不足。三、以相关方理论为基础,以支付意愿法为工具,研究了药品不良反应补偿起付级别、起付金额、最高补偿额、相关方责任承担分配、补偿资金筹资方式、资金管理方式、政府作用等,并以企业为研究对象,分析了影响企业对不同损害患者补偿影响因素的研究,弥补了前人研究中理论分析较多而实证研究较少的不足。总的来看,本文不仅从比较中分析了药品不良反应补偿体系中各要素,而且对各个要素进行了进一步的研究与分析,提出了因果关系判断的新的量化方法与标准、损害分级的初步研究方法与分级标准、而且还利用支付意愿调查法,分析了反应补偿起付级别、起付金额、最高补偿额、相关方责任承担分配、补偿资金筹资方式、资金管理方式、政府作用等,并进行了实证分析,并得出了一些有意义的结论。研究的结果对于构建我国药品不良反应补偿制度促进我国社会保障制度的健康发展、科学地制定相关政策来规范和引导相关方社会责任承担具有重要的理论价值和现实意义。更多还原

【Abstract】 The human beings have a history of several thousand years in applying medicine to cure diseases. As a dominant tool for preventing and curing diseases, medicine plays a significant role in securing human health and promoting the development of social civilization. But meanwhile, in the process of applying medical drugs which are hoped to function for medically treating the diseases, there have been occurrences of harmful effects which are irrelevant and even contrary to the objective of using the drugs. In the last century, the incidents caused by unproperly using thalidomide, sulfanilamide elixir and etc. set off the alarm to prevent prople from ADR. The incidents of negative impacts by LongDanXieGan pill、puerarin injection, houttuynia injection, and etc. occurring in recent years in China further indicate the“double-edged sward”feature characterized by medical drugs. Namely, medical drugs have the function of preventing and curing diseases, but meanwhile would also cause unexpected harmful reaction irrelevant or contrary to the treatment objective. In real life, the increasingly more ADR incidents of body damages as well as the disputes or law suits because of ADR set drug’s reasonable application in dilemma.In abroad, since German’s Thalidomide Incident happened in 1957, Germany, the United States, Japan, Sweden, and Taiwan region in China have established ADR compensation systems relevant to resolve damages caused by medical drugs. However starting from 1988 domestically, we have only been trying to implement the monitory work on the Adverse Drug Reaction (hereinafter referred to as ADR), on the basis of introducing the experience from abroad. Despite of increasingly more incidents of adverse reaction to drugs occurred recently, the establishment of such a compensation system hasn’t been set on agenda. In 1989, the Monitory Center was established by the Ministry of Health for the purpose of monitoring ADR cases and, in March of 1989, officially joined WHO’s international cooperation center for monitoring drug application. In 1999, this Center began to be administered by the State Drug Administration. In November of the same year, the monitory and ADR management measures(trial) were promulgated. In 2001, a feedback system was built up and put into service to reflect ADR situation and, meanwhile, relevant monitory centers were founded in 31 provinces and cities throughout China by 2002. In March of 2003, ADR monitory and management measures to were formally put into practice and has currently been formed into an ADR network monitory and reporting system from various regions to the state level throughout out China. Nevertheless, a system for compensating negative effects caused by medical drugs hasn’t yet been put on the agenda. Some domestic scholars, with reference to the existing systems abroad, appeal for the establishment of relevant compensational systems. In this regard, this paper will begin with the establishment of ADR compensation systems and then analyze or compare such systems’key factors both abroad and at home. Furthermore, a deep analysis will be adopted using AHP, willingness to pay (WTP), multi-element linier regression and other methods to expound and prove each of these factors possibly existing in the proposed system for drug negative effects. All this is aimed at providing options for the government to choose when it decides on establishing or implementing such compensational systems.Firstly, as focused on the purpose of establishing an ADR compensation system, my research applies a comparative method to analyze the each phase of currently existing systems at home and abroad and illustrates what needs to be improved in the proposed system. We’ve realized from the research that specific laws need to be defined beforehand to back up the establishment of such a system, on the basis of which, compensation will be properly applied to the recipients or beneficiaries who are entitled to. Besides, financial aspect is a significant factor for the compensation system, such as fund management and where it comes from. Other factors like the relation between drug and affected patients, verification of damage extent, compensation criteria, and etc. are also important factors for the system. According to the current domestic situation, there is a blank area in this respect as China has no specialized law to regulate or manage the compensation for drug damage. Therefore, the research work relevant to such system’s key factors has almost been blank. This paper reveals some potential factors to consider for the purpose to lay a solid foundation for later phases of work.Secondly, through AHP and composite index analysis in the research, my goal is to resolve the issue into various component factors and then leverage their relations to each different level, forming a hierarchical structure model to be applied to analysis and comparison. Eventually, The study obtained the important weight effect that the factor at the lowest level has to the height one. Based on the algorithm using composite index method, a standard has been obtained to judge the cause-effect relation. From the research, analyzing tools such as hierarchical and composite index methods can absorb some relevant factors causing ADR, meaning that qualitative description could be converted into quantitative data through proper conversion. Meanwhile, particular factors could be easily inserted into the calculation model and the extent of cause-effect correlation between the damage and drug. The whole judgment process is simply easy to implement at finger tips. This paper will further elaborate on the process to verify the affirmative results.Thirdly, none-coefficient inspection and multi-element regression analysis are based on the theoretical background from the willingness survey. The discovery from such research shows that, regardless of how serious the damage is, the relevant parties tend to select a certain level of damage as the base for compensation. This fact reflects that all the parties involved have same attitude for compensation but with a different base for compensation. It also explicitly explains the different standpoints for each of the relevant party involved. Through a verification process, the government institutions are thought to be set to compensate at a higher threshold base. The drug manufacturers should be set at a lower threshold while drug merchandizing (pharmacies) or applying institutions at the lowest. Thus, more damaged parties would be fit into the scope of compensation. In case of defining the compensation amount, relevant parties usually have lower willingness for compensation for damages less serious than class 5 whereas the curve for such willingness shows a sharp turn when damages are at class 4 or 3, indicating the change of willingness for compensation as well as a clearly increased amount for financial compensation. When damages are more serious than class 3, there is a linier change on the curve between damage level and compensation amount, demonstrating an amount of 300,000 at least in case of death. As for the responsibilities to be held by the parties involved, drug manufacturers and government institutions should hold the major responsibilities. Drug merchandizing (pharmacies) or applying institutions should be less responsible while the damaged parties should not be responsible in any case. As far as the fund source is concerned, there is a need to build up a multi-level or multi-channel model. It is unpractical to let one single party bear all the compensation responsibilities. Through the analysis conducted on government duties, the government should not be out of holding responsibilities and be involved in establishing compensational systems. For example, drug manufacturers hope that government should hold certain ratio of responsibility for damages while the government only agrees to finance certain amount of leading fund for establishing the system. This indicates a differentiation in the standpoint among the parties involved in the case. After applying the multi-element logistic regression model to analyze the factors influencing the compensation at various levels, the influential factors are different with the damages of various classes being regressed. For instance, when damages are of class 7 with“a”equal to 0.05(a=0.05), the influential factors in the model are different; the comparison between the damage classes from 7 to 1 indicates that the number of influential factors in the model is decreasing while the extent of damage gets more serious. This demonstrates manufacturer’s willingness for compensation if a compensation system is established.Fourthly, the classification for the extent of ADR damages is the basis for constituting an ADR compensation system. This classification must be defined and is unavoidable. On one hand, it is helpful for building up the whole salvage system. On the other hand, it will serve as a criterion to be referenced during the process of compensation. Furthermore, some statistical methods and models are also applied in the research, with the damages being described in 6 classes. Finally, after a scoring process by experts and statistical calculation, a quantified classification table is initialized for defining ADR classes.Fifthly, how to manage the financing process is also a compulsory question to be considered for establishing the ADR compensation system. During the research, the principle-agent theory is used as the base. In scenario one, the agents’profits either through hard working or duty shirking must be higher than the (opportunity) costs from the analysis, while agents’performance can be supervised by the principle. Otherwise, agents would not accept to perform the task whereas the government has to handle it internally. In scenario two, when the principle can not supervise agents’performance, we suppose“p”as the probability for agent’s hard working and“q”for duty shirking behaviors. In case of agent’s costs and risks not off setting its gains, once a hard-working agent finds out that the agency is unprofitable, the agent would then loose its motivation for performaning the task. Therefore, whether an agent would accept the deal still depends on the profit. When the agent has only one task to perform, it’s decision also depends on its personal gains, while the decision process is more complicated.Lastly, this paper elaborates on the related factors and the theoretical functions for establishing in China a compensation system as well as the relevant policy proposal.The paper’s creative point of views is reflected in the following three respects;1. Through mathematical and statistic methods, the judgment methods and standards for the cause and effect of Adverse Drug Reaction are newly constructed , filling the blank area in this regard both at home and abroad.2. Through the quantification standards constructed for defining the damage extent caused by Adverse Drug Reaction, it is expected to divert the former judgment by damage characteristics to quantification judgment.3. With related theories as the base and willingness-to-pay method as means, this paper is focused on studying the compensation classification and the base or maximum amount for compensating the damages caused by Adverse Drug Reaction. The paper also illustrates the responsibility distribution of related parties, channels to raise compensation funds, management of the funds, government roles and etc... With enterprises as the core objects being studied, the paper analyzes the influential factors that affect enterprises’compensation to the damaged parties, thus offsetting the inadequacy where more theoretical analysis but fewer studies have been conducted by the predecessors.On the whole, this paper does not only analyze the various factors that could exist in the suggested system to compensate for Adverse Drug Reaction, but also studies and analyzes each of the factors. The paper proposes new quantification methods and standards to judge the cause-effect relation and initial studying approaches as well as classification for damage classes. It also utilizes willing-to-pay method to analyze compensation levels, minimum or maximum amount for payment, responsibility distribution of related parties, fund raising channels, fund management, and government roles. Based on analyzing the examples in real life, the paper generates some meaningful conclusions. The researches herein represent the significant theoretical value and practical meaning for constituting a compensation system for Adverse Drug Reaction, for promoting healthy development of the social welfare system, and for scientifically stipulating related polycies to regulate and guide social responsibilities held by relevant parties in China.更多还原