Abstract
摘要:轉譯科學主要包括兩個主要成份:知識的轉接與技術的轉移。知識的轉接為將在實驗室的基礎科學之發現成功地轉變成為增進人類福祉的實際應用。技術轉移為將針對某一領域所發現出的科技轉移至另一個不同的領域。例如轉譯醫學即為自工作檯至病榻的醫藥研究,其目的在將基礎實驗室的發現應用在預防、診斷及治療疾病上。另外,銜接性試驗即為評估在某一地區所研發出的新藥是否適用於不同人種地區的臨床試驗。在完成人類基因體計畫之後及近年來生物技術的突破性發展,疾病的治療或基因改造作物/食品之研發均可以分子為標靶。鑑於對基因的分子機轉之突破性的發現與瞭解,轉譯科學可縮短生醫及生技產品的研發時間並提高在實際應用的成功率。因知識轉接為評估前面研發階段所得的發現是否可成功地轉譯進入目前研發階段的成功性。所以知識轉接著重於預測與推廣。另外技術轉移則在探討處理與領域的交互作用。雖然轉譯科學在生技產品研發扮演非常重要的角色,但目前有關轉譯科學的統計方法學相關文獻十分不足,所以本計畫為一個為期三年的研究計畫,針對下列轉譯科學議題進行統計方法學的研究 (1)人類乳突病毒疫苗療效評估 - HPV疫苗預防病毒感染能力對於子宮頸癌預防療效的預測能力之評估 (2)疫苗免疫力銜接性評估 - 疫苗的血中免疫抗體對疫苗療效的預測能力之評估 (3)臨床結果對等性評估 - 基因表現量對等性對臨床結果對等性的預測能力之評估 (4)銜接性試驗評估 - 新藥在成年人的療效對兒童療效的預測能力之評估 (5)新藥研發 - 第一、二期臨床試驗結果對第三期臨床試驗成功性的預測能力之評估 (6)生物製劑學名藥之評估 - 藥劑生物平均對等性對療效對等性的預測能力之評估,及(7)基因轉殖作物/食品與傳統非基轉作物/食品的實質對等性之評估。本計畫所提出的統計方法均將以模擬研究探討其型Ⅰ誤差與檢定力。另外並將以實際數例介紹本計畫所發展出的統計方法。
Abstract: Translational science consists of two major components: knowledge transition and technology transfer. Knowledge transition involves successful conversion of basic scientific discoveries obtained from the laboratories into practical applications for improvement of the wellbeing of human society. For example, translational medicine is the “bench-to-beside” research which applies a basic laboratory discovery to prevention, diagnosis, and individualized treatment of a certain disease. On the other hand, technology transfer is the transfer of a technology developed for a certain area to another area. For example, bridging studies evaluate whether an innovative drug developed in one region can be transferred into another region with a different ethnic background. After completion of Human Genomic Project and availability of breakthrough biotechnology, most of applications such as treatment of a certain disease and development of a genetic modified organism (GMO) can be targeted at the molecular levels. Armed with breakthrough discoveries and better understanding of the mechanisms at the molecular levels of genes, translational science can shorten the duration of product development and may has a better chance of success in practical applications. Since knowledge transition is to evaluate whether the discoveries obtained at the previous stage of the development can be also successfully translated into the current stage, this involves prediction and generalization. On the other hand, technology transfer comprises of treatment-by-area interactions. However, although translation science is crucial in development of biopharmaceutical and biotechnology products, very scarce literature on statistical methodology for translational science are currently available. Hence, this three-year research proposal will be devoted to develop the statistical methodology for evaluation of translation science in the following areas: (1) efficacy of HPV (human papillomavirus) vaccine – predictability of the cervical cancer prevention based on the prevention of HPV infection, (2) vaccine immunogenicity bridging studies – predictability of vaccine efficacy based on its immunogenecity, (3) equivalence of clinical outcomes – predictability of equivalence in clinical outcomes based on equivalence in gene expression levels, (4) bridging evaluation – predictability of the efficacy of a new drug for the children between 2 and 12 years of age based on the efficacy results from adults between 20 and 64 years of age, (5) drug discovery and development – predictability of the success of the late phase III trials based on the results of early phase I and/or II trials, (6) biosimilar or follow-on biologics - predictability of clinical equivalence for generic biological products based on average bioequivalence, and (7) GM crops or food - evaluation of substantial equivalence of composition profiles between GM crops or food and their conventional counterpart except for inserted traits. Simulation studies will be conducted to evaluate the size and power of the proposed methods. In addition, the proposed methods will be illustrated with the real data.
Keyword(s)
銜接
轉移
轉接
交互作用
推廣
Bridging
Transfer
Transition
Interaction
Generalization