BACKGROUND: Adjudication is a standardized, objective, and often blinded mechanism designed to assess clinical events with increased accuracy. It is performed by a centralized committee of independent reviewers, who are specialized, expert physicians who have no involvement with either the treatment of study subjects or the trial sponsor. Adjudication can decrease variability and bias in study results and increase the likelihood of correct identification, assessment, and categorization of clinical events such as potential malignancies diagnosed through histopathology. Histopathology is highly variable due to the subjective nature of the assessments. THESIS: If it is the case that there are clinically significant discrepancies between local and central diagnoses and that central adjudication yields more accurate diagnoses than a local pathologist, then it should be accepted that adjudication ought to be more widely used in clinical trials to assess histopathology-related safety outcomes and endpoints. METHODS AND STATISTICS: This is a retrospective cross-sectional study assessing interrater variability between local and central diagnoses of biopsy samples in a clinical trial setting using kappa scores and percent agreement. Certified Professional Coders (CPC) and central pathologists used the International Classification of Diseases for Oncology revision 3 (ICD-O 3) to codify the local and central assessments to permit comparison. Three statistical groups (group A: the full dataset, group B: pathology sub-specialty reading groups, and group C: non-melanoma skin cancers versus all other malignancies) were assessed for interrater variability in seven separate analyses: neoplasm versus non-neoplasm (analysis 1), benign versus malignant including non-neoplasms (analysis 2.1), benign versus malignant excluding non-neoplasms (analysis 2.2), discrepancies in morphology and/or behavior including non-neoplasms (analysis 3.1), discrepancies in morphology and/or behavior excluding non-neoplasms (analysis 3.2), all discrepancies leading to differences in treatment (analysis 4.1), and all discrepancies leading to difference in treatment with round 1 matches removed (analysis 4.2). RESULTS: 602 cases comprised the dataset. Based on kappa scores, there is near perfect agreement between the central and local lab diagnoses in analyses 1, 2.1, and 2.2 in group A (all cases in the dataset). The percent agreement for these analyses is above 90%. The group A (full dataset) kappa score and percent agreement decreased to 0.59 and 68.3%, respectively, in analysis 3.1 (discrepancies in morphology and/or behavior codes, including non-neoplasms). When non-neoplasms were removed (analysis 3.2), the kappa score and percent agreement were 0.52 and 57.0%, respectively. In group C, NMSC had substantial kappa agreement in analyses 1, 2.1, and 2.2, whereas all other malignancies had near perfect kappa agreement. All percent agreements were above 88% and surpassed the minimally acceptable threshold for interrater percent agreement in healthcare (80%). Group B divided the data set into 10 sub-specialty reading groups. Kappa scores ranged from 0.66 (GYN) to 1.00 (lung) in analysis 1; the analysis 1 kappa score for lymphoma was 0.55, but this was not statistically significant. In analysis 2.1, lung and sarcoma had the highest kappa scores (1.00) and dermatology and GYN had the lowest (0.71). As in analysis 1, the kappa score for lymphoma was 0.55 but was not statistically significant. When non-neoplasms were removed from analysis 2.2, 6 of the 10 sub-groups had kappa scores of 1.00, but all 6 had sample sizes less than 10. Percent agreement ranged from 80 to 100 percent. When all cases were considered regardless of number of rounds of review (analysis 4.1), about 90% of diagnoses would have similar courses of treatment. All sub-groups except sarcoma reached the minimally acceptable agreement rate in healthcare (80%). In the remaining 33% of cases that did not have matching diagnoses in round 1 (analysis 4.2), 34% may have different courses of treatment depending on whether the local or central diagnoses was used. Mid-study updates to the charter and CPC/reviewer manuals and processing of specimens did not have a significant impact on results. CONCLUSION: Although there is little discrepancy between local and central pathologists on whether malignancies exist among samples, there is discord regarding specific diagnoses and their associated treatments. Adjudication can assist in decreasing this discordance in order to develop the most specific and accurate safety profile for a compound.

As the bio-pharmaceutical industries find itself moving forward in super high speed, the more strategic move it need to take to keep it survival in the biotechnology competition.The big pharm starts to release new drug exploring,investigation,production,and marketing and try to take the contract research method to run their business.Thus the Contract Research Organization (CRO) find its wave in the bio-pharmaceutical industries. The CRO in Taiwan is a young competitor.The CRO business is a knowledge-based incentive business.It takes medical human resources and stastics experts to make it run .It needs to qualify the national regulation while the clinical trial related regulations in Taiwan needs to qualify the international good clinical trial regulations.This study focuses on the competitive forces analysis of the CRO industries in Taiwan. The study will review the lately development of CRO companies in Taiwan.The study will review the company profile and analyze it in the Diamond model by Michael Porter. The government factor plays a significant role in the Clinical trial related business.The CRO will be more flexible and competitive under preper regulations.

No description available.

The core of biotechnological industry is biomedical products which are related to health and life and need clinical trial. Laboratory data are collected during different stages of clinical trial. Laboratory data are provided by laboratories which are accreditated internationally. Most of medical laboratories in Taiwan are not accreditated. This exploratory research is to understand the change of healthcare envirovement and the stratege of accreditation to be taken when we develop the biotechnological industry which needs to be accreditated. We used questionare as a tool and mailed 616 and received 152. The statistical methods are descriptive and nonparametrical statistics. The results show as following: 94.7% of the responders agreed to have Taiwanese own medical laboratory accreditation system which should be approved by the Department of Health. The surveyors of hospital accreditation are appraised. Most of the responders (89.5%) did not agree the replacement of professional peer review by physicians without clinical laboratory training. The quality and quantity of CNLA surveyors need to be improved. Continous quality improvement gets concensus of the responders. The certification of accreditation shall connect to the payment system of national health insurance but does not equal to good clinical laboratory. Most of the responders (88.8%) recognized that implementing medical laboratory accreditation system is a part of organization learning. ISO 15189 medical laboratory accreditation is the first choice of the responders (50.7%) and CAP-LAP is the second (28.3%). The reasons for implementing and not implementing medical laboratory accreditation system are improving quality and the change of hospital accreditation, and just applying hospital accreditation and not required by law. Key words¡Ghospital accreditation, ISO 15189:2003, CAP-LAP, program for improving biotechnology industries, contract research organization, business strategy, organization learning.

昂貴的藥物研發成本，促使製藥生技產業的委外營運模式，以合約方式提供在藥物研發過程中專業化服務的產業，而近年來由於委外研發服務的高效率，已明顯縮短了新藥開發的時程；同時，在全球醫藥研發服務產業的市場中，約有超過七成的收益來自於臨床試驗服務；由此顯見醫藥研發服務產業中的臨床試驗部分的重要性。 醫藥研發服務是個高度國際性競爭的產業，如何找到發展的核心利基以突破重圍，是許多後進企業或國家所必需面對的嚴峻考驗。因此，本研究主要描述台灣目前的醫藥研發服務產業以及臨床試驗產業發展概況，並探討台灣是否具備發展臨床試驗產業的實力。透過本研究，希望對於台灣發展臨床試驗產業，或是推動台灣成為亞太臨床試驗中心，都能提供作為規劃與執行時的參考資訊。 本研究重要結論與建議如下： 1. 以新藥研發價值鏈而言，台灣目前在每一個階段的工作均已佈局，其中又以臨床試驗階段最有潛力加入國際的競爭市場；長期而言，為追求醫藥產業最大的經濟效益，應強化國內的基礎研發工作，進而刺激與培養國內醫藥研發服務產業的能量。 2. 產業政策的落實不能只談邏輯架構或觀念，應該設定明確的推動方案、目標與達成時間表，要推動產業必須貫徹以管理的觀念；同時也應加速業者與官方之間的溝通協調，其中包括藥政主管單位對於產業發展應由被動轉為積極主動的角色，另外，政府部門跨部會的整合也是相當重要的。 3. 國內的全民健保制度涵蓋了所有醫療資源的運用，而健保制度的設計缺乏鼓勵預防與醫藥研發的投入的機制。因此建議應深入分析與探討健保對於產業的影響，進而能以更積極正面的態度促進製藥生技或醫藥研發服務產業的發展。 4. 建議國內可以由政府與製藥產業界共同出資，成立具有公信力且目標明確的教育訓練組織，提供以實務為導向且有系統的在職教育，用以規劃與培植國家未來所需要的專業臨床試驗人才。 5. 建議國內應就醫療院所執行臨床試驗相關作業訂定管理原則，包括臨床試驗贊助款的管理與運用規範、相關執行人員的權利義務等，藉由透明化的標準與明確的獎勵制度，提高醫師與醫院參與臨床試驗的動機；同時也應鼓勵醫院設立專責的臨床試驗辦公室，執行各項協調、整合與管理的工作，並促進與產業界間的互動。 / The cost of drug research and development has soared during the past years. And this compels pharmaceutical and biotechnology companies to look for new, smarter ways of running their businesses. One of their strategies is trying to accelerate drug development by outsourcing. The size of the outsourcing market for Contract Research Organizations (CROs) is rising. Clinical-trial operations hold over 70% of the revenue in the CRO industry. Competition in the CRO industry is extremely international in scope. The key issues for the catching-up company or country is to find their own niche. This study goes on to identify and profile the development of clinical trials and the CRO industry in Taiwan. It also seeks to identify ways of showcasing Taiwan as an Asia-Pacific Clinical Trail Service Center. There are several conclusions from this study: 1. In the value chain of new drug discovery and development, the current status in Taiwan has the potential to join the international market by conducting the clinical trials. In the long term, we should consolidate our basic medical research to pursue the maximum benefit of biotechnology and pharmaceutical industry, and then to enhance the capability of CRO in Taiwan. 2. The policy for improving industry must be set up after the explicit acting plans, goals and time schedule. It should go through with management, not just a structure or concept. We have to hasten the communication between industry and government. The medical legal authorities need to be more active. Ultimate integration of the functions of the related government departments is exceedingly important. 3. The National Health Insurance (NHI) system covers all of the medical resources in Taiwan, but it lack for the incentive to encourage the medical research. It is recommended that NHI Program should probe into the impact of the biotechnology and pharmaceutical industry, and then try to revise it with more positive thinking. 4. It is very important for Taiwan to improve the professional in clinical trials. Setting up a training center funded by both government and industries is strongly recommended. The organization will have the definite goals and accountability, and provide practical training and systematic continuing education. 5. We need more regulating operations of clinical trials of hospitals in Taiwan. These operations should include the usage of the fees from sponsors, and the rights and responsibilities of all staff. We should set up a transparent standard and obviously encourage a mechanism to enhance the motivation of physicians and hospitals to participate in clinical trials. Hospitals should be encouraged to establish an independent office for clinical trials to perform all the details. This office will promote the interaction within the industries.

Contract Research Organization (CRO) industry has been a fast growingservice sector within the pharmaceutical and biotechnology industry since the early 1980’s. Aiming at assisting its clients in obtaining product registration and market approval from the health authorities (i.e. Food and Drug Administration of the US and Department of Health of Taiwan), CRO’s provide extensive consultations as well as clinical research and management services, covering both pre-clinical and clinical arenas. In recent years, global CRO’s have been expanding towards the Southeastern Asian (thereafter “SEA”) region targeting, Singapore, Taiwan, Hong Kong, China, and South Korea. While most of the empirical research on market entry mode has targeted the manufacturing industries, more recent studies have been completed on service sectors targeting advertising and financing industries. Since the history of CRO is relatively short, limited study has been performed on this industry, especially on the international entry patterns and behaviors for the CRO industry. This research document examines the current environments of CRO industry in Taiwan and Singapore and the factors influencing international company’s decisions on the entry mode. A recommendation of the best options to enter Taiwan and Singapore for the international CRO’s is presented. The paper concludes with findings as well as recommendations for further investigation directions.

在生技服務產業中，臨床試驗服務業(CRO)為收益最佳且最具發展價值的項目，2009年全球CRO總營收中，臨床試驗服務業營收就約占總營收的一半，加上近來全球各國開始加速醫藥產業的發展，國際藥廠也逐漸加重臨床試驗外包比例，整體全球臨床試驗服務產業需求大增。 台灣自1997年起，本土企業就開始努力耕耘於臨床試驗服務領域，直至今日，已累積許多成功的經驗與案例，然而在面對國際大廠寡占市場，以及亞洲新興國家CRO企業如雨後春筍般盛出的環境下，台灣CRO企業於發展上仍飽受壓力，不過，這些在多年的經營下，事實上也已累積了相當的能力，若能針對自身核心能耐進行統整分析、經營及拓展，相信仍將有辦法面對全球之競爭環境。此外，由於臨床試驗服務業屬知識密集之服務性產業，經驗累積、專業性及外部關係資產等智慧資本皆較有形資本更能代表企業所具之價值，因此，本研究主要從智慧資本的角度來探討臨床試驗服務企業所具有之核心能耐，並依不同經營時期比較核心能耐之變化，以了解企業所具有之競爭優勢及優勢變化。一方面期望透過本論文之架構，提供企業有關自身核心能耐之分析方式的參考，協助其進行自我核心能耐之統整分析，另一方面，也期望藉由本論文之CRO企業核心能耐之個案分析，提供企業在選擇經營或拓展核心能耐時作為參考。 本研究所得到的結論如下： 1. 運用外部關係資本-與其他企業進行聯盟合作，是臨床試驗服務公司用以提升服務能力、擴大服務範圍，及拓展核心能耐的重要方式。 2. 臨床試驗服務公司所具明確的企業價值與文化，有助於其營運上的發展以及獨有特色的創造。 3. 發展較成熟的臨床試驗服務公司會具備涵蓋人力資本、組織結構資本及顧客關係資本之核心能耐，所具備之核心能耐較不易再進行拓展，反之，較新進的臨床試驗服務公司則較易拓展其核心能耐。 4. 臨床試驗服務公司所擁有的「教育」及「品牌」智慧資本，有助於提升公司其他的智慧資本。 5. 我國本土臨床試驗服務公司較重視發展具差異性之核心能耐，而我國外商臨床試驗服務公司則較重視員工專案執行之能力。 關鍵詞：臨床試驗服務產業、CRO、核心能耐、智慧資本 / In the Bio-service Industry, clinical trial service is the most profitable and valuable item. In 2009, the revenue of clinical trial service accounted for about half of the revenue of CRO Industry. Recently, since all the countries in the world are speeding up developing Pharmaceutical Industry and pharmaceutical companies are gradually raising the proportion of clinical trial outsourcing, the demand of clinical trial service are grately increasing. From 1997, Taiwan local companies have been working so hard in the clinical trial service area. Till now, Taiwan local companies have accumulated lots of successful experience. But when facing the oligopoly market of CRO Industry and competition of Asia new CRO companies, Taiwan CRO companies still have big stress on operation. However, since Taiwan CRO companies have had great competence in clinical trial service, we believe that if Taiwan CRO companies can tidy up, analyze and expand their own core competence, the competitive strength of Taiwan CRO companies will get improved to face the global competition. Besides, intellectual capital of CRO companies which are knowledge intensive business services (KIBS) shows real value of the CRO companies. Hence, this study is trying to investigate the core competence of clinical trial service companies from intellectual capital aspect, and also trying to compare the differences of the core competence in the different timing. We hope this study can on the one hand provide CRO companies a way to analyze their core competence, and on the other hand can provide the successful core competence information of the study cases for CRO companies as a reference. There are several conclusions from this study: 1. Using relationship capital-business collaboration is an important way for the clinical trial service companies to improve their service ability, broaden their service area, and develop their core competence. 2. The clear values and culture of clinical trial service companies can help the development and operation of the companies, and create the characteristic of the companies. 3. A mature clinical trial service company has accumulated plentiful core competence in human capital, organizational capital and customer capital, and it’s hard for the company to deepen and broaden its core competence. Relatively, it’s easier for a young clinical trial service company to develop its core competence. 4. The intellectual capital of “Education” and “Brands” of clinical trial service companies can upgrade other intellectual capital of the companies. 5. Taiwan local clinical trial service companies emphasize the core competence with differenciation while foreign clinical trial service companies in Taiwan emphasize good executive ability of the employee. Keywords: Clinical trial services, CRO, Core competence, Intellectual capital

生物醫藥產業對人類健康福祉影響甚鉅，同時也屬於技術、資本密集、開發期長、風險偏高的產業，在新藥開發的歷程中，臨床試驗是開發中藥品自「試驗階段」邁向「市場階段」的絕對關鍵過程，其重要性不言而喻。對藥廠而言，臨床試驗若能有效率地被執行，一方面可縮短試驗時間減少花費；另一方面則是搶得先機佔據市場，及早實現獲利。因應臨床試驗重要且繁複需求的臨床試驗服務公司（Contract Research Organization, CRO）便應蘊而生。 CRO產業在美國的發展已逾40年，在奠基於過去的競爭基礎之外，其CRO產業已朝向「便利性」與「客製化」等利基市場佈局，以滿足新的顧客價值主張，並創新商業模式，追求新的成長機會。本研究在介紹美國CRO之產業市場營運模式之外，也以個案分析方式，自國內CRO公司與藥廠/生技公司的互動、合作，探討CRO的營運模式是否符合客戶需求，並嘗試以<白地策略>書中四個核心市場要素：顧客價值主張、利潤公式、關鍵流程與關鍵資源，思索CRO公司應如何經營市場白地。希望借鏡國外CRO公司的演進，反饋予國內CRO產業的未來發展及策略調整參考。 / Bio-pharmaceutical industry on human health well-being highly influential, but also a industry of technical, capital intensive, long development periods, and high risk. Among the course of drug development, clinical trials are absolute the key to the process, and advance the development process from the pilot phase to the market phase. For pharmaceutical companies, if the clinical trial can be executed efficiently, they can shorten the test time and spending; seize the market in advance, and reap profits as soon as possible. In response to the important and complex clinical trial requirements, the Contract Research Organization (CRO) prospers and takes advantage of a favorable situation. The evolvement of the CRO industry in US is more than 40 years. In the foundation base in the past, the CRO industry has been towards convenience and customization and other niche market distribution, to meet new customer value propositions, innovative business models and pursue new growth opportunities. In this thesis, the author not only introduces the CRO’s business models in US, but also explores the CRO’s business models in Taiwan by way of case studies. Through the interaction and cooperation between domestic pharmaceutical companies and CROs, the author wants to find out if the business models of CROs are in line with customer needs. The author also wants to quest if the CROs can learn how to manage and operate a white space which the CROs hope to seize by way of the book Seizing the White Space lists four fundamental building blocks including customer value proposition, profit formula, key resources, and key processes that make a company business model works. The domestic CROs can adjust their strategy and business model for fitting customer’s value proposition.