澳門大學碩士學位論文 Abstract During the past century, medical products have witnessed a high incidence of misadventures. Some typical events examined are: Elixir of sulphanilimide (1930s'), Thalidomide (1960s'), Diethylstilbestrol (1960s') and PPA (1990s'). ADR (Adverse Drug Reacations) has become a significant problem in drug safety management due to its high incidence, inevitability and unpredictability. Based on pharmacovigilance and pharmacoepidemiology research, many countries, when carrying out risk management, have adopted Benefit-Risk analysis of marketed medical products. ADR monitoring in our country is now in its infant period, while it faces serious social problems. In consideration of a large population, restricted condition and standard of medical treatment of our country, ADR events analyzed have been provided with common features of large number of affected patients, severe influences and high treatment expenditures. We have a large variety of medical products; especially we lack special research on herbal medicine ADR, and therefore, with existing resources, we may not find proper measures to proceed to extensive safety assessment of marketed drug. Part from this, some of our medical institutions, pharmaceutical companies and healthcare professionals do not have enough acknowledgement of ADR, which greatly impacts the ongoing ADR monitoring programme. With limited number of medical safety specialists in our country, drug benefit-risk analysis is held back at a great extent. However in recent years, the public has been paying much attention to drug safety, such as PPA event, Long Dan Xie Gan Wan event, Astemizol incident, etc., all of which have brought about certain drug panic among the public. Currently, enhancement of drug safety surveillance is in increasing needs by the public and ADR surveillance methods need to be updated accordingly. By discussing and introducing advanced experience in international drug risk-management, esp. in pharmacovigilence, this essay aims at developing applicable methods and strategies for Chinese ADR surveillance, and further paving the road for national ADR monitoring development. This essay consists of six parts: Part I: With bibliography analysis and comparison, this essay explores the background, purpose, structure and method of this research, and re-defines the terminologies and terms referred to in this essay. All these facts show ADR surveillance is essential to the society, and our current ADR monitoring system is greatly differ from the common pharmacovigilance system that many countries employ. 3 國際藥物警戒現狀與中國藥品不良反應監管髮展 Part II: compare the common pharmacovigilance system applied in different countries in terms of report systems, sources, scopes, requirements, assessments, information feedback and sanction mechanisms, and common a feature, spontaneous report, is found in their pharmacovigilance systems, while in other aspects, they differ a lot. Part III: this essay introduces the current situation and tendency of pharmacovigilance in UMC, ICH and CIOMS, and it finds out that these international organizations have contributed a lot to ADR surveillance globalization, standardization and eletronization and international coordination as well. Therefore, competent authorities, pharmaceutical companies and medical institutions in many countries have participated in their programmes. Part IV: by analyzing existing article, this essay introduces the pharmacovigilence system of some countries, such as U.S.A., UK, France and Japan, and further discuss about their legal basis, application and development. To draw the result, to protect the patients' privacy and improve the report quality has become the greatest challenge to European and American competent authorities. In EU countries, the monitoring method has gradually transferred form post-marketing inspection to pharmacoepidemiology research; while in U.S.A., pharmacoepidemiology research has been replaced by risk management aiming at improving the quality of report and introducing new methods or risk reduction. Part V: by the means of analyzing articles and site inspection, this essay probes into the current situation and problems of our national ADR surveillance, and compares previous and current ADR monitoring measures and concludes the new method is greatly improved than previous one. However, it still needs improvement in its availability, practicability and criterion. The ADR surveillance has developed fast and stepped onto a new stage in recent years and built up a nationwide monitoring network. Reports received increase rapidly, but the development of this system is hold back due to limited professionals, funds and relative legal regulations. Part VI: with the methods of comparison investigation, development analysis and SWOT analysis, this essay touches upon the topics of building ADR aiding system in our country, evaluating the unreported reasons of spontaneous report system, professional training and individual report, and further discuss the experience that we should learn from international pharmacovigilance. Part from that, this essay also takes our national situation into consideration and combine them with international experience to develop ten strategies for our national ADR surveillance. Keywords: Pharmacovigilanc, ADR, spontaneous reporting, safety evaluation 4

澳門大學碩士學位論文 中文摘要 近一個世紀以來,藥害事件屢次發生,典型的有20世紀30年代的磺胺 劑事件、 60年代的沙利度胺(反應停)事件、己烯雌酚引起下代少女陰道癌事件以及90年代末 期的PPA 藥害事件。藥品不良反應因其高發率、不可避免性和不可預期性,成為用 藥安全的重要隱患。以藥物警戒和藥物流行病學研究為主體的藥品上市後風險/效益 評價已經成為世界各國藥品風險管理的發展趨勢之一。 我國的藥品不良反應監管盡管起步較晚,但是卻面臨著非常複雜的社會現實問 題。我國人口基數大,醫療條件和醫療水平有所侷限,導致了不良反應受害群體大、 影響程度深、相關治療支出費用高等問題;我國的藥物品種多,中藥的不良反應問題 更是缺乏研究,導緻難以利用有限資源進行廣泛的上市後安全性評價:我國的醫療機 構、生產企業、衛生人員不良反應意識淡漠,嚴重影響了藥品不良反應監測工作的開 展;我國缺少專業化人才,導致難以開展藥品風險/效益評價工作等。然而近年來, 公眾普遍加強了對藥品安全的關注,如PPA 事件、龍膽瀉肝丸事件、“息斯敏”風 波等引起了一定的藥品安全恐慌。公眾對於加強藥品安全保障的訴求迫使我國藥品不 良反應監管必須與時俱進。 本論文主要是通過借鑒國際先進的藥品風險管理經驗尤其是藥物警戒的經驗,取 長補短,探討適合我國國情的不良反應監管制度與方法,從而為國家藥品不良反應監 管提供發展思路和發展策略。 本論文分為六個部分進行探討: 第一部分,主要通過文獻分析、比較研究等方法,探討該研究的背景、目的、框 架、方法,並且對論文涉及的術語進行規範,結果表明進行藥品不良反應監管是非常 有必要的,我國現行的不良反應監管體系與國際上普遍的藥物警戒體系有所異同。 第二部分,主要從報告制度、報告來源、報告範圍、報告要求、報告處理、信息 反饋、處罰機制上比較了國際上主要國家現行的藥物警戒制度,結果表明自發報告制 度是目前藥品不良反應監測制度的主流方式,但是在其他方面各國家之間有所差異。 第三部分,綜述國際藥品不良反應監測組織、人用藥品註冊技術國際協調會議、 國際醫學科學組織理事會等三個國際性組織的藥物警戒現狀與趨勢,結果表明此三個 國際組織在藥品不良反應監測的國際化、標準化、電子化和國際協調中起到了重要作 用,得到了許多國家行政當局、公司、醫藥學協會的認可和參與。 第四部分,通過文獻分析的辦法主要介紹美國、歐盟地區、英國、法國、日本等 1 國際藥物警戒現狀與中國藥品不良反應監管髮展 主要國家地區的藥物警戒體系,分別探討了其藥物警戒的法律基礎、實施現狀與發展 趨勢。結果表明病人的隱私保護、提高報告的質量已經成為歐美各行政當局的主要挑 戰。歐盟國家藥物警戒手段從上市後藥物監測向藥品流行病學方法應用轉移;美國藥 物警戒手段從藥品流行病學評價向風險管理轉移,著重提高報告的質量以及開發更多 的風險干預工具等。 第五部分,通過文獻分析和實地考察的辦法探討了我國藥物不良反應監測現狀與 存在的問題,並且對新舊藥品不良反應監測管理辦法進行了比較。結果表明,新的藥 品不良反應監測管理辦法相比前版而言有了很大的進步,但是在可獲得性、實用性、 規範性等上仍需進一步配套和改進。我國的藥品不良反應監測體繫近年來取得了長足 的髮展,已初步建成了全國的藥品不良反應監測網絡,報告的數量上得到了很大的提 升,然而人才的缺少、资金的缺乏以及缺少相關的法律配套等制約了發展。 第六部分,通過比較研究、發展性研究、SWOT分析等方法,就建立我國藥品不 良反應救濟制度、自發報告系統漏報原因分析、專業人員培訓、個人報告等相關主題, 探討國際藥物警戒工作對我國的啟示和借鑒。此外,還結合中國國情,提出了十條發 展策略。 關鍵詞:藥物警戒 藥品不良反應自發報告 安全性評價 2