2011-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/678322摘要：自人類基因體計劃完成後，許多突破性技術如微陣列、單核&#33527;酸多型性、轉譯RNA剖析等均已應用在體外診斷醫療器材的研發上。這些新一代生技的體外診斷醫療器材包括偵測遺傳指標的藥物遺傳及遺傳檢驗試劑、多變數指標的體外檢驗試劑、癌症診斷之基因表現剖析系統試劑或代謝酵素基因定型系統試劑。因為體外診斷醫療器材之臨床研發成本較藥物的為低而時間亦較短，故體外診斷醫療器材是在台灣生技產品中較具潛力且看好的一個重要領域。雖然體外診邊療器材的品質非常重要，但是目前有關體外診斷醫療器材的特性表現評估之統計方法學的文獻十分缺乏。因此本專題研究計畫將針對體外診斷醫療器材之統計評估的理論與方法學進行研究。專題研究三年計畫共包括三部份:(a)精密度之評估 (b)鼻用氣膠器與噴霧器之體外生物相等性評估與(C)線性與線性範圍之評估。針對體外診斷醫療器材支線性與線性範圍之評估，針對體外診斷醫療器材的精密度，我們將根據CLSI EP5-A2準則，導出檢定試劑內變異及實驗室變異小於事前訂定之規格的統計檢定方法。針對鼻用氣膠器與噴霧器的體外生物相等性評估，我們將應用修正大樣本方法及廣義樞紐量導出美國食品與藥物管理局準則中的線性標準之95%信賴上界。我們將根據CLSI EP6-A準則及平均線性偏差，線性偏差平方和及線性偏差差異系數等線性評估標準提出決定濃度的個數及濃度的相對距離之統計方法。另外，我們將嘗試提出決定樣本數的方法亦將執行模擬研究評估各種所提出方法的型I誤差率與檢定力。我們亦將以實際數例介紹所提出各種方法之應用。<br> Abstract: After completion of Human Genomic Project (HGP), many breakthrough technologies, such as microarray, single nucleotide polymorphism (SNP), mRNA transcript profiling, etc., have been employed to develop in vitro diagnostic devices (IVD). This new class and generation of IVD includes pharmacogenetic tests and genetic tests for heritable markers, in vitro diagnostic multivariate index assays, expression profiling test system for cancer diagnosis, and drug metabolizing enzyme genotyping system, and many others. On the other hand, IVD is the most promising area for biotechnology and biopharmaceutical industry in Taiwan due to its relatively inexpensive cost and short duration for clinical development. Despite of its emerging importance for biotechnology industry in Taiwan and as well as in the world, few attention has been paid to statistical evaluation of the performance and characteristics of IVD. In this three-year project, we will develop statistical methods on the design and analysis in the following three areas: (a) evaluation of precision, and (b) evaluation of bioequivalence of nasal aerosols and nasal sprays, (c) evaluation of linearity and linear range. For evaluation of precision, under the design recommended by the approved guideline EP5-A2 of Clinical Laboratory Standard Institute (CLSI), we will develop testing procedures for determining whether the within-device variation and between-laboratory device are within the pre-specified limit. For evaluation of bioequivalence of nasal aerosols and nasal spray, due to nuisance parameters involving with mean and variances, we will apply the modified large sample (MLS) method and the method of the generalized pivotal quantities (GPQ) to derive the upper confidence limit of the linearized criteria proposed by the guidance of the US Food and Drug Administration. For evaluation of linearity and linear range of IVD, we will develop statistical methods for determination of the number of concentrations and intervals and spacing between concentrations under the design suggested in the approved CLSI guideline EP6-A of with respect to different criteria for evaluation of linearity such as average deviation from linearity (ADL), sum of squares of deviations from linearity, and coefficient of variation of deviations from linearity (CVDL). In addition, sample size estimation will be explored. 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.體外診斷醫療器材精密度體外生物相等性線性In vitro diagnostic devicelinearityprecisionbioequivalence