「被忽視」的熱帶疾病(NTDs)中的寄生蟲疾病(Parasitic Diseases; PDs)除對非洲人群健康之危害甚鉅外，並進而對非洲地區社經體系造成嚴重衝擊與造成巨大的「失能調整人年」損失。由於不易取得治療PDs傳統基本藥物的問題，許多非洲民眾便以其部落社區的傳統治療師所採用的傳統草藥來進行PDs的治療，雖然這些傳統草藥容易取得，但是成分的內容和藥效品質甚或產生嚴重的致命副作用。雖然TRIPS協定第31條和杜哈宣言的第五和第六段對於製藥能力不足或大部分皆無製藥能力的貧窮國家，可以基於「國家緊急危難或其它緊急狀況」的事由，以強制授權方式取得專利藥或較便宜的學名藥以解決造成國家危難的特定公共健康事件，但是國際大藥廠認為無利可圖，不願意花費資金投注於預防或治療此類疾病藥物的相關研發外，高收入的國家為保護其大藥廠的藥物專利，也往往使用一些經濟制裁手段逼迫上述國家就制定國內專利法以保護其藥物專利。雖然經杜哈宣言修正TRIPS協定第31(f)條有關強制授權對外出口的障礙，但是出口國對於強制授權程序與是否能取得政治上和藥廠業者的支持，仍充滿困難。應用「專利池」可以減少交易成本或法律爭議而可調和「強制授權」與解決「權利耗盡」的爭議，有助於解決非洲開發中國家取得專利藥物的困境。PDs造成非洲開發中國家民眾失能等長期痛苦與健康生活損失，類推適用SARS模式，可依TRIPS協定第31條(b)與杜哈宣言第五段(c)將之視為「造成國家緊急危難或其它緊急狀況」的重大公共健康的事由而可行使強制授權。雖然「生醫專利池BVGH」的「非獨家個別授權與免授權費」的操作模式與傳統電信技術專利池不盡相同，但因藥廠不願投入治療PDs的傳統基本藥物存在的副作用與抗藥性的新藥研發，為鼓勵對治療PDs的藥物進行創新研發， BVGH彈性的授權方式與免繳交授權費，將有利於解決開發中國家未來取得新專利藥的困境。除BVGH外，建議結合全球獎勵基金以「激勵拉拔」的方式獎助願意投入治療PDs新藥研發並將專利自願授權給BVGH的藥廠。鑒於全球暖化與最近中東難民潮大量湧進歐洲，罕見的PDs可預期會大量傳播開來，將嚴重衝擊歐洲等先進國家良好的公共衛生體系，而使得「NTDs尤其是PDs不再只是專屬於貧窮國家的疾病，亦將常現於富有的先進國家」。這些NTDs疾病將提供藥廠進行新藥研發的利基，然而在未來可能產生專利池的反競爭問題，導致支配市場獨占性的隱憂值得關注。 / Parasitic diseases (PDs) not only cause the huge health hazards to African populations, but also they further severely impact on African socio-economic system as resulting in huge economic and health losses as assessed by disability adjusted life-years. Since it is not easy for Africans to access the essential medicine to treat PDs, many of them will seek for the help of local healers in tribal communities to treat PDs. Although these traditional herbs are readily available, the content and quality of drug ingredients may even cause serious fatal side effects. Poor countries with insufficiencies or lacks of the pharmaceutical capacities may still access the patented medicines or cheaper generics to solve the national crisis caused by the specific public health events through compulsory licensing (CL) based on "national emergency or the other emergency situations" according to TRIPS Article 31 and Doha Declaration on the fifth and sixth paragraph due to that the large international pharmaceutical companies consider unprofitable, unwilling to spend money to invest on the research and development (R&D) of new drugs for prevention or treatment purpose. Moreover, the high-income countries also tend to exert some of the economic sanctions to force those poor countries to enact national patent law in order to protect drug patents. Furthermore, the mandatory obstacle of exportation authorized by CL from the amended TRIPS Agreement Article 31 (f) by the Doha Declaration has been improved; nevertheless, it is still fraught with difficulties in utilization of CL for the exporting countries because this should be dependent on whether they may actually get the supports from political and the pharmaceutical industry. Application of patent pools model may benefit to reduce transaction costs or legal dispute thus reconciling and resolving issues related to CL as well as doctrine of patent exhaustion and that it is beneficial to help solve dilemma for African countries to access patented drugs. Because Africans severely suffer from disabled caused by PDs thus leading to long-term pain and health life losses, African countries can grant CL as PDs may be regarded as national crisis like SARS causing "national emergency or the other emergency situations" as authorized from TRIPS Agreement Article 31 (f) and Doha Declaration paragraph 5 (c). Although the practice of individual licensing with royalty-free for BVGH is somewhat different from that of traditional patent pools, this licensing practice mode is beneficial to innovation in new drugs R&D to improve the side effects and drug-resistance of traditional essential medicines and help African countries to access patented new drugs in the future. Finally, it is recommended to cooperate with Award Foundation to encourage incentive for pharmaceutical companies which contribute most to new drugs R&D and voluntary licensing to BVGH. Owing to global warming and recent emergence of huge refugees into Europe rare PDs will be obviously spread out thus causing severe impacts on well-established public health system as leading to emergence of PDs in developed countries like Europe. Altogether, such situations definitely provide a good incentive in new drugs R&D for pharmaceutical companies; however, it guarantees concerns on anti-competitive and monopoly issues derived by biomedical pools in the future.

【研究緣起與問題】2003年春季，SARS在全球造成一陣轟動，同時也重創全球的經濟，如今SARS會不會再來？政府如何因應？政府如何監測疫情？如何防治疫情？如果SARS等新興及再浮現感染症 （Emerging and Re-emerging Infectious Diseases）出現時，負責全國傳染病防治任務的行政院衛生署疾病管制局是如何作好全國傳染病防治工作呢？中央及地方主管機關之溝通，如何共同消除指責與誤會，發揮團隊精神，如何共同作好全國傳染病防疫任務，爭取公眾對政府之瞭解並加以支持，同時防止任何可能之攻擊，才是全民之福祉。故以「全國傳染病通報系統」的績效，其所仰賴之溝通通路之問題研究，是本研究的動機。了解「傳染病通報管理系統(WEB版)」最大的問題及新興傳染病（如SARS）防治通報的問題及「傳染病通報管理系統」最需要改進之的地方，是本研究的目的。 【研究方法與資料】本研究採取量化與質化並重的方法，以網路問卷方式的進行問卷調查，問卷對象為全國使用傳染病通報管理系統之相關人員，問卷問題內容的設計主要的型式含有開放式問卷（Open –Ended Question）、封閉式問卷（Close-Ended Question）及混合型問卷（Mixed Question）三種。同時以九十二年針對新興傳染病SARS期間為例，深度訪談當時任職於中央與地方負責傳染病防治權責具代表性者五位主管進行訪談，瞭解受訪者對新興傳染病如SARS防治的問題及「傳染病通報管理系統」最需要改進之的地方，以彌補問卷調查法無法深入瞭解到問題之缺點。 【研究結論與建議】 一、根據筆者初步研究經問卷的實證調查之後，從問卷分析資料顯示，使用者使用電腦的時間愈久，對以新版為溝通工具滿意度愈低；而愈瞭解通報系統的使用者，其以新版為溝通工具滿意度愈高，愈滿意新版改進之電腦網路溝通效果。顯示新版的通報系統在設計的操作介面與程序上，沒有人性化，作業內容繁多、需輸入的項目、資料太繁瑣、版面太繁瑣等，反而徒增使用者的困擾；而愈瞭解通報系統的使用者，其對新版的滿意度越高，表示對於使用者在操作上的教育訓練仍須加強，才能發揮新版通報系統的成效。 二、從敘述統計分析中發現： 受訪者對「訊息異動通知作業流程滿意」的使用滿意度的平均數最高，平均數為2.8095表示：較為滿意。「通報作業流程滿意嗎」的使用滿意度的平均數最低，平均數為2.3934，受訪者表示：較為滿意。以新版為溝通工具整體溝通滿意情形，平均數為2.558滿意。 三、開放式問卷分析資料顯示，花太多時間、速度太慢、網路的頻寬過窄又不穩定或無法登錄、作業內容繁多、作業流程問題、資訊管理問題及功能增添與建議等部分。 四、根據筆者初步研究深度訪談之後，彙整中央主管機關及地方主管機關的訪談核心二部分的問題與建議。 五、研究建議： 綜合問卷調查及深度訪談結果，提出政策層面、組織溝通層面、管理層面、實務操作層面等之建議。 【關鍵字】傳染病通報系統、嚴重急性呼吸道症候群(severe acute respiratory syndrome, SARS)、組織溝通、溝通通路、行政院衛生署疾病管制局 / 【Background and Issues】 In the spring of 2003, SARS outbreaks devastated the whole world; they also heavily damaged the world economy. Will SARS come back? How can governments manage it? How can government monitor the epidemics? How can we control the infection? When emerging and re-emerging infectious diseases such as SARS appear, how can the Center for Disease Control of the Department of Health, an organization in charge of national disease control, plan and execute measures for the control of communicable diseases? Effective communication between the central and the local competent authorities to remove together blames and misunderstanding, to develop team spirit, to attain jointly the goal of disease control, to solicit understanding and support of the public to the government, and to prevent any likely attack are some of the considerations in improving the welfare of the public. The reason of the present study was to understand, through the achievements thus far of the National Communicable Disease Reporting System, issues involved in the communication channels. The purposes of the study were to understand the major problems of the Communicable Disease Reporting and Management System (the Web version), issues involved in the reporting of emerging infectious diseases, and areas of the Communicable Disease Reporting and Management System where improvement was most urgently needed. 【Method and Materials】 Both the quantitative and qualitative methods were used. Questionnaire interview was conducted through the web to persons using the Communicable Disease Reporting and Management System throughout the country. The questionnaire contained open-end questions, closed-end questions and questions of mixed types. At the same time, to understand in depth areas not properly covered by the questionnaire interview, five key persons responsible for disease control at the time of the SARS outbreaks in 2003 at the central and the local levels were interviewed to understand their attitudes toward the control of emerging infectious diseases such as SARS, and the improvement most urgently needed for the Communicable Disease Reporting and Management System. 【Results and Recommendations】 1. Preliminary findings from analysis of the questionnaire interview showed that users became less satisfied with the new version communication means the longer they were in use of computers. Users who knew more about the use of the reporting system were more satisfied with the new communication means, were at the same time, more satisfied with the communication effects of the improved version. These facts suggested that the new reporting system was less user-friendly in the designing of interface and procedures. The system required more work, more detailed inputs, and thus added additional burdens on the part of the users. The more the users understood the reporting system, their satisfaction was higher, indicating that, for the new version reporting system to function in full, training of the users in the use of the system should be strengthened. 2. From the descriptive analysis, it was found that the average score of user satisfaction on the “information change reporting procedures” was as high as 2.8095, suggesting that the users were fairly satisfied. The satisfaction score on “reporting procedures” was the lowest at 2.3934. The overall satisfaction score on the use of the new version as a communication means was 2.558. 3. Findings from the open-end questions gave the following recommendations: taking too much time, too slow, frequency of the web too narrow, unstable, and unable to load, too detailed, issues related to operational procedures, issues related to information management and additional functions, etc. 4. By analysis of the in-depth interview, some issues were raised and recommendations made to the central and the local competent authorities. 5. Through questionnaire survey and in-depth interview, some recommendations concerning policies, organizational communication, management and practical operation were made. 【Key Words】 Communicable Disease Reporting System, SARS (Severe Acute Respiratory Syndrome), organizational communication, communication channels, Center for Disease Control, the Department of Health

本研究的內容，主要是以居住在大台北地區20歲以上之就業者為研究對象，藉著問卷調查的方式，從需求面來探討消費者對重大疾病保險的看法與期許。分析方法分別為次數分配、因素分析、Cronbach α、單因子變異數分析、交叉分析。 本研究將保險購買評估準則，利用因素分析將之區分為「公司狀況與產品利益」、「過去與週遭經驗」、「保費及公司型態」、「感情與服務態度」及「專業能力」等五個因素。並探討各因素在購買經驗及人口統計變數上是否具顯著差異。另外分別針對購買和理賠經驗、購買動機、購買意願、資訊來源、人口統計變數與產品利益屬性等方面做卡方（χ2）獨立性檢定。研究發現： 1.就保險購買評估準則方面： 最受重視的是「公司狀況與產品利益」，其次則為「過去與週遭經驗」，而最不受重視的則為「保費及公司型態」。 2. 購買重大疾病保險之經驗、原因與資訊管道 （1）受訪者中投保重大疾病保險的比例有六成以上，整體而言，已婚者購買的比例大於未婚者；而隨著收入的增加其購買重大疾病保險的比例也增加。 （2）未購買及中斷購買原因主要是「保費負擔太重」、「對保障內容不滿意或不瞭解」以及「已有全民健保就足夠」。 （3）購買資訊管道以「保險業務人員的推銷」、「親友的介紹」以及「公司的團體保險」為主。 3. 產品利益屬性 （1）對於重大疾病保險未來發展方向的選擇，以「增加重大疾病的項目」、「結合其他醫療功能的保單」以及「增加給付方式的選擇」等三項為大部分受訪者的選擇。 （2）保險金給付的偏好方式，以一次金給付、分次終身給付及代付醫療費用三者之接受度最高。 （3）適當的重大疾病給付額度，大多數的受訪者認為應在101∼300萬之間。 / This study focus on labor people aged from 20 in metropolitan Taipei arena. By questionnaire interviews, we will study the customers' opinions and expectations to dread disease insurances from market demand. The analytical methods will be described as followings: Frequency Distribution, Factor Analysis, Cronbach α, One-Way Anova Analysis and Crosstable. The study classifies the purchasing evaluation criteria of insurance as five factors such as “Cooperation situation and product profit margin”, “Past and surrounding experiences”, “Insurance premium and cooperate types”, “Emotion and service attitudes” and “Professional”. And explores the possibilities of the apparent differences for each factor to purchasing experiences and demographic variables. On the other hand; we try to make χ2 independence evaluation to purchasing & reimbursement experiences, purchasing motivation, purchasing intention, information resources, demographic variables and product profit properties. We found: 1.The evaluation criteria of buying insurance: People more emphasize on “Cooperation situation and product profit margin” and followings by “Past and surrounding experiences”. And less emphasis on “Insurance premium and cooperate types” 2.The experiences, results and information channels for purchasing serious disease suffered insurance: (1)The proportion of holding policy for serious disease is 60% or above. Generally speaking, the proportion of married people policyholder is larger that the one of single people. And the more the income increases;the more the proportion of purchasing disease suffered insurance increases. (2)The main reasons of not purchasing or quitting are “Premiums are too expensive”, “Not really satisfy or understand the contents of insurance covered”, and “It’s quite enough for having public healthy insurance”. (3)The main information channels to purchase insurances are “The promotion of insurance sales people”, “Relatives & friends introduction”, and “Cooperation group insurance”. 3.Product profit properties: (1)For the options of dread disease insurance development, generally, there would be three items to be acceptable such as “Additional benefits of dread diseases”, “Combine with policies of other medical functions”, and “Additional options of payment mode”. (2)The preferred payment way of premiums will be “Pay off”, “Life Amortization ”, and “Pay medical expenses by agent” and more acceptable. (3)Most interviewees think that the reasonable benefit amount for dread disease insurance will target on between NT$1 million and NT$3 million.

本論文的研究目標是建構一個由多標記複合成的最佳疾病診斷工具，所考慮的評估準則為操作者特徵曲線在特定特異度範圍之線下面積(pAUC)。在常態分布假設下，我們推導多標記線性組合之pAUC以及最佳線性組合之必要條件。由於函數本身過於複雜使得計算困難。除此之外，我們也發現其最佳解可能不唯一，以及局部極值存在，這些情況使得現有演算法的運用受限，我們因此提出多重初始值演算法。當母體參數未知時，我們利用最大概似估計量以獲得樣本pAUC以及令其極大化之最佳線性組合，並證明樣本最佳線性組合將一致性地收斂到母體最佳線性組合。在進一步的研究中，我們針對單標記的邊際判別能力、多標記的複合判別能力以及個別標記的條件判別能力，分別提出相關統計檢定方法。這些統計檢定被運用至兩個標記選取的方法，分別是前進選擇法與後退淘汰法。我們運用這些方法以選取與疾病檢測有顯著相關的標記。本論文透過模擬研究來驗證所提出的演算法、統計檢定方法以及標記選取的方法。另外，也將這些方法運用在數組實際資料上。 / The aim of this work is to construct a composite diagnostic tool based on multiple biomarkers under the criterion of the partial area under a ROC curve (pAUC) for a predetermined specificity range. Recently several studies are interested in the optimal linear combination maximizing the whole area under a ROC curve (AUC). In this study, we focus on finding the optimal linear combination by a direct maximization of the pAUC under normal assumption. In order to find an analytic solution, the first derivative of the pAUC is derived. The form is so complicated, that a further validation on the Hessian matrix is difficult. In addition, we find that the pAUC maximizer may not be unique and sometimes, local maximizers exist. As a result, the existing algorithms, which depend on the initial-point, are inadequate to serve our needs. We propose a new algorithm by adopting several initial points at one time. In addition, when the population parameters are unknown and only a random sample data set is available, the maximizer of the sample version of the pAUC is shown to be a strong consistent estimator of its theoretical counterpart. We further focus on determining whether a biomarker set, or one specific biomarker has a significant contribution to the disease diagnosis. We propose three statistical tests for the identification of the discriminatory power. The proposed tests are applied to biomarker selection for reducing the variable number in advanced analysis. Numerical studies are performed to validate the proposed algorithm and the proposed statistical procedures.

科学研究費補助金 研究種目:試験研究(B) 課題番号:05556021 研究代表者:大澤 俊彦 研究期間:1993-1995年度