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研究生: 宋嘉祥
CHia-hsiang Sung
論文名稱: 應用受試者操作曲線下的面積及Youden指數比較兩個相關生物標記之研究
指導教授: 陳玉英
Yuh-Ing Chen
口試委員:
學位類別: 碩士
Master
系所名稱: 理學院 - 統計研究所
Graduate Institute of Statistics
論文出版年: 2015
畢業學年度: 103
語文別: 中文
論文頁數: 45
中文關鍵詞: Youden指數ROC聯合信賴域二元常態分布
外文關鍵詞: Youden index, ROC joint confidence region, bivariate normal
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  • 利用生物標記進行疾病診斷是目前醫學上一個重要的課題,根據生物標記正確地將病人判斷為患者的機率為真陽率 (True-positive rate;TPR),反之,將健康者誤診為患者的機率為偽陽率 (False-positive rate; FPR)。在可能的生物標記臨界值之下,真陽率相對於偽陽率的曲線即為該生物標記的受試者操作曲線(Receiver Operating Characteristic curve; ROC curve)。此外,真陽率與偽陽率的最大差異,為Youden指數,記做J。傳統上利用此一曲線下的面積(Area under the ROC curve; AUC)評估生物標記之診斷效率。本文為比較兩個服從二維常態分布生物標記在診斷疾病的效率,建立AUC 差異及 J 差異的聯合信賴域。當生物標記的分布未知時,本文也利用自助法(Bootstrapping method)建立AUC差異及J差異的無母數聯合信賴域。除了藉模擬方法研究上述聯合信賴域的覆蓋機率,也利用CA19-9及CA125兩種生物標記在診斷胰臟腫瘤的資料說明本文所提聯合信賴域的應用。


    To do diagnosis based on biomarkers is an important issue in medicine study. The true-positive rate (TPR) is the probability of a patient diagnosed to be ill and the false-positive rate (FPR) is the probability of a healthy person diagnosed to be ill. Under all possible cut off points of a biomarker, the curve of TPR vs. FPR is called the Receiver Operating Characteristic curve (ROC curve) of the biomarkers. Moreover, the maximum difference between TPR and FPR, called the Youden index, denote as J. The area under the ROC curve (AUC) and the Youden index are conventionally used to evaluate the efficiency of the biomarkers. To compare the efficiency of two biomarkers that are distributed according to a bivariate normal distribution, we construct a joint confidence region for the difference of AUC and that of Youden index. When the bivariate distribution of the two biomarkers is unknown, we suggest construct a nonparametric joint confidence region for AUC-difference and J-difference based on the bootstrapping method. In spite of studying the coverage probability of the confidence regions mentioned above based on a simulation method, we also use two biomarkers, CA19-9 and CA125, to diagnose the pancreatic cancer based on the proposed confidence regions.

    摘要 i Abstract ii 致謝辭 iii 表目錄 v 圖目錄 vi 第一章 研究動機及目的 1 第二章 文獻回顧 5 2.1 AUC及J的推導及估計 5 2.2 Faraggi二維常態分布資料之轉換 8 2.3 二維廣義伽瑪分布 9 第三章 AUC差異與J差異之聯合信賴域 11 3.1 有母數方法 11 3.2 無母數方法 18 3.3 信賴域的面積及二維常態分布適合度檢定 20 第四章 模擬研究 23 4.1模擬設計 23 4.2模擬結果 24 第五章 實例分析 26 第六章 結論與討論 30 參考文獻 32 附錄 34

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