最近幾年為加速藥物的上市，且面臨各區域受試者數量之不足，各國政府及藥廠開始對多區域臨床試驗感興趣，而多區域臨床試驗是指不同地區或國家同時加入的一項臨床試驗，為此日本厚生勞動省提出兩個準則來判定此臨床試驗之藥物對某地區是否具有療效。本研究考量在多區域臨床試驗中不同區域之異質性，發展一延伸自日本指引之替代準則，並進一步推導其統計特性。電腦模擬研究證明我們提出的替代準則可以提供充分且一致的證據於評估某特定區域之療效。本研究並使用一真實資料來解釋此方法的執行。

In recent years, in order to accelerate the release of drugs and  increase the statistical power of clinical trials, many governments and pharmaceutical industries have become interested in conducting multiregional clinical trials (MRCTs). A MRCT is defined to enroll subjects from many countries/regions in the clinical trial. In 2007, the Japanese Ministry of Health, Labour and Welfare (MHLW) has proposed a guideline of MRCTs to determine whether the drug is efficient in a particular region. Based on the Japanese guideline, this research proposes an alternative criterion with consideration of the heterogeneity among different regions. The corresponding statistical properties are derived. Computer-simulated studies prove that our proposed criterion can provide sufficient evidence for evaluating the effect of a specific region. A real data is used to explain how to apply this method.

目錄
一、介紹	1
二、多區域試驗模型	4
2-1 統計模型	4
2-2 全域假設檢定	5
2-3 區域有效	7
三、真實例子	10
四、方法模擬	15
五、討論及結論	30
六、參考文獻	33
附錄1	41
附錄2	43
 
圖目錄
圖1.令μ_Y=1.8,2.0,2.2；σ_(Y_p)^2=2,6,10；f_(Y_p )=f_(X_p )=0.1,0.3,0.5,
0.7,0.9；μ_X=1；σ_(Y_1)^2=σ_(Y_2)^2=σ_(X_p)^2=σ_(X_1)^2=σ_(X_2)^2=6，所算出的保證機率。	15
圖2.令μ_Y=1.8,2.0,2.2；σ_(Y_p)^2 =2,6,10；f_(Y_p )=f_(X_p ) =0.1,0.3,0.5,
0.7,0.9；μ_X=1；σ_(Y_1)^2=σ_(Y_2)^2=σ_(X_p)^2=σ_(X_1)^2=σ_(X_2)^2=6所算出來的π，來進行模擬後的保證機率，跟利用理論算出來的保證機率的差距直方圖。	17
圖3.令μ_Y=1.8,2.0,2.2；σ_(Y_p)^2 =2,6,10；f_(Y_p )=f_(X_p )=0.1,0.3,0.5,
0.7,0.9；μ_X=1；σ_(Y_1)^2=σ_(Y_2)^2=σ_(X_p)^2=σ_(X_1)^2=σ_(X_2)^2 =6；π=0.2,0.5,0.8比較使用日本方法一(點線)及Chen[10]文章內的方法(實線)跟本文的方法(虛線)，並對比其差距。	18
圖4. 令μ_(Y_1 )=μ_(Y_2 )=1.8,2.0,2.2；μ_(Y_p )=1；σ_(Y_p)^2 =2,6,10；f_(Y_p )=f_(X_p )=0.1,0.3,0.5,0.7,0.9；μ_X =1；σ_(Y_1)^2=σ_(Y_2)^2=σ_(X_p)^2=σ_(X_1)^2=σ_(X_2)^2=6，將在藥有療效的情況下算出來π的帶入並模擬出區域保證機率為何。	31
圖5.算出來的檢定力跟進行模擬研究出來的檢定力其之間的差距直方圖。	37 
表目錄
表1.Conner 成人 ADHD資料變化量表的描述性統計。	10
表2.將π代入0.2、0.5、0.8所算出來托莫西汀對台灣是有效的保證機率。	13
表3.令療效差異為0.8、1.0、1.2；設定在特定地區使用實驗藥的變異數為2、6、10；特定區域佔總實驗人口比為0.1、0.3、0.5、0.7、0.9，並算出能使得特定區域其保證機率能等於0.8的π。	20
表4.假設除了特定區域服用測試藥的受試者以外，變異數皆為6，並且特定區域服用測試藥的受試者療效的變異數令為2,6,10，而受試者服用測試藥的療效效果為1.8,2.0,2.2，安慰劑效果為1，令p區佔總試驗人數比例為0.1,0.3,0.5,0.7,0.9，令π=0.2,0.5,0.8，來測試此方法跟日本方法一以及Chen文章內所提供的方法算出來的
p區保證機率差別。	23
表5.令受試者服用兩種藥物的療效差異為0.8、1.0、1.2；設定在特定地區使用實驗藥的變異數為2、6、10；特定地區p佔總實驗人口比為0.1、0.3、0.5、0.7、0.9，並判斷使用理論算出來的跟模擬驗證出來的整體區域檢定力是否相同。	35
表6.令其他區域的受試者服用兩種藥物的療效差異為0.8、1.0、1.2，特定區域則認定為其地區受試者服用兩種藥是沒有差別的；設定在 地區使用實驗藥的變異數為2、6、10；p地區佔總實驗人口比為0.1、0.3、0.5、0.7、0.9，利用設計階段時的π，代入藥實際無效的地區，所算出的保證機率。	38

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