摘要:慢性病毒性肝炎及肝細胞癌影響國人健康甚鉅,如何預防及治療仍有許多問題亟待解決。舉例而言,雖然經由全國 B 型肝炎疫苗接種已經成功預防國人 99%青少年以及嬰幼兒的 B 型肝炎病毒感染,在成年人 B 型肝炎帶原率仍高達12−20%,而且僅 30-50%患者可透過現有抗病毒藥物加以控制,不易根除。約 30%慢性 C 型肝炎無法藉由目前標準治療根治。肝細胞癌是國內最常見的肝臟惡性腫瘤,每年約有 2000 人新診斷個案,但除了少數早期患者可以接受手術根治性切除以外,目前對此癌症欠缺有效的治療方法。此外,非酒精性脂肪肝病和藥物引發肝傷害將成為國內重要肝臟疾病,需要積極研究及預防處理。 雖然國內已有許多專家學者投入肝臟疾病的研究並獲得不錯的成果,僅以個人或單一家醫院要進行臨床試驗收案速度將極為緩慢,能收集的組織檢體也很有限。為了加速新藥及新醫療器材之臨床試驗以及相關研究的進展,成立國內肝炎及肝細胞癌臨床試驗合作聯盟有其迫切性。我們在「行政院國家科學委員會生技醫藥國家型科技計畫」資源中心下申請計畫,前三年已建立台灣肝炎及肝癌之臨床試驗合作聯盟[Taiwan Liver Disease Consortium (TLC)],以協助研究者及產業界推動肝病相關臨床研究及試驗。本計畫同時收集臨床檢體,以應未來轉譯醫學研究之需。 在前三年計畫中,我們首先結合北部(臺大醫院總院暨雲林分院、台北榮總、國泰醫院、亞東醫院、仁愛醫院、慈濟醫院台北分院、基隆長庚醫院、及林口長庚醫院)、中部(中國醫藥大學附設醫院、台中榮總、及中山醫學大學附設醫院)、南部(高雄長庚醫院及高雄醫學大學附設醫院)以及東部(慈濟醫院花蓮總院)等14 家醫學中心成立臨床試驗核心,並整合基礎研究、統計學、病理學、流行病學、以及資料庫管理等各領域專家協助合作聯盟臨床試驗之運作。我們已經成立由七位專家組成的指導委員會(工作推動小組)負責評估審查本聯盟主導或協助進行之所有臨床試驗或研究。在各醫學中心,我們透過研究助理或護理師負責各中心與進行臨床試驗有關之所有事務。此外,我們建立一個標準流程有系統地自各合作醫院收集肝病病人的臨床、病理及流行病學的相關資料及臨床檢體,並據此建立一個臨床資料庫及血清檢體庫,未來可進行轉譯研究。我們過去三年期間協助推展 19 個國際藥廠主導的多中心臨床試驗,協助 7 個本土生技公司或藥廠主導的多中心臨床試驗,並負責 4 個 TLC 主持人發起之臨床試驗的進行。我們未來三年期間將協助推展 20-25 個國際藥廠主導的多中心臨床試驗,協助 5-10 個本土生技公司或藥廠主導的多中心臨床試驗,並負責 5-10 個 TLC 主持人發起之臨床試驗或研究的進行。此外我們也已經建立一個網頁,公開廣泛介紹本試驗合作聯盟之架構、成員、功能及運作方式。未來將進一步設計次網頁及聯結,讓有興趣藥廠以及研究者可以對這個試驗合作聯盟有所了解以及產生興趣。 我們相信這是亞太區域以及國內一個大型針對肝臟疾病所成立的臨床試驗合作聯盟,結合各大醫學中心及研究機構內所有對肝病研究有興趣的基礎和臨床學者成立一個研究網絡 (research network),協助進行國際藥廠所主導或是主持人所發起的臨床試驗,並加速國內產業界對新藥、新器材的研發工作。本合作聯盟試驗之成效以及透過網頁之宣傳,將能有效吸引國際大藥廠來本土進行新藥、新器材的投資,本土生技公司或藥廠開發新藥物。我們同時將建立肝病的資料庫及檢體庫,相信對台灣肝病的轉譯研究將會有極大的助益。
Abstract: Chronic viral hepatitis B and C and the related liver diseases (liver cirrhosis and HCC) are still major health problems in Taiwan. Furthermore, after the eradication of chronic viral hepatitis, nonalcoholic fatty liver diseases and drug-induced liver injury will become the next most common etiology of liver diseases in Taiwan. Overall, we, as physician scientists, have the mission to solve these important health problems through the development of new drug/device and the conduction of translational researches. Thus multicenter trials supported by international or local bio-pharmaceutical companies as well as investigator-initiated clinical studies/trials (IITs) are needed. Current problems in conduction of clinical trials or translational researches include: (1) inadequate interactions between basic and clinical researchers, or among clinical researchers, certain new information or new products could not be incorporated into clinical trials; (2) lack of novel idea, the young clinical investigator may have difficulty in identifying important issues to be addressed; (3) difficult to identify cooperative team, lack of a research network for collection of clinical patients and samples; (4) difficult to collect, store and manage data and serum/PBMC samples; (5) for translational researches, lack of input and cooperation from basic scientists; and (6) particularly for clinical trials, lack of research resources support, including research assistants, laboratory support, preparation of IRB process, etc. Besides, there are now many strong competitors in the Asia-Pacific region. Without cooperation, the recruitment of patients will be slow, and the competitive edge will be low. Thus we urgently need to establish a research network for liver diseases in Taiwan to help incorporating and facilitating the related research and development activities. The resolution of certain clinical issues actually can be accomplished through the development of a cooperative team or consortium composed of clinical investigators and experts in various aspects of biomedical researches. To solve the aforementioned problems, we develop “Taiwan Clinical Trial Consortium for Hepatitis and Hepatocellular Carcinoma” (abbreviated as Taiwan Liver Disease Consortium [TLC]). In the past three-year project, we successfully form a consortium for conduction of clinical trials and develop the platform for collection of clinical information/serum bank for future translational research. We develop the steering committee for review and monitoring of all multicenter clinical trials or clinical studies covered by the TLC. We have recruited capable research assistants distributed in active study sites for the preparation and conduction of all clinical trials-related activities and jobs. We already help the conduction of 19 international company-sponsored multicenter trials, 7 local biopharmaceutical company-sponsored clinical trials, and 4 investigator-initiated clinical trials. We have also developed a webpage demonstrating the organization, composition and function of the consortium. In the next 3 years, we plan to help the conduction of 20-25 international company-sponsored multicenter trials, 5-10 local biopharmaceutical company-sponsored clinical trials, and 5-10 investigator-initiated clinical trials/studies. Through this platform, clinicians can translate any novel idea into clinical trials, can easily identify the research partners, and the complicated process of trial including IRB application can also be settled through the help of research assistants and the resource center of NRPB. We establish an efficient and productive research team to solve important liver problems in Taiwan, and to promote the research activity and academic performance. In the future, we can provide clinical samples for translational research. At the same time, the network will cooperate with local or international pharmaceutical company to develop new drugs or devices. Furthermore, through the propagation of our consortium in website, more investment, either locally or internationally, on liver diseases-related new drug and device will be attracted into Taiwan. We believe that after the development of the consortium, the following long-term objectives will be achieved, including promotion of Taiwan liver research to be one of the world leaders, acceleration of the new drug or device developed by local Taiwan pharmaceuticals for liver diseases, provision of clinical samples for future translational research in liver diseases, and promotion of the health of Taiwanese people by reducing liver-related morbidity and mortality.